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Index

https://t.me/med1917

δβ Thalassemia 11

α2β1integrin αIIbβ3 complex α-granules defects 258

Thalassemia 7

Thalassemia 7–8

α thalassemias 7–9

Thalassemia 7

Thalassemia 7–8 mutations that cause 9 variants

aceruloplasminemia 185 activated signaling, AML 40–41

c-KIT 41 FLT3 (FMS-like tyrosine kinase 3) 40–41

acute GvHD acute lymphoblastic leukemia (ALL), 67–82;

B-ALL subtypes basic helix-loop-helix (bHLH)

B-cell precursor 69

BCL11B-driven ALL 78–79 BCR::ABL1 positive ALL

CAR-T cell therapy 374–375 CDX2/UBTF ALL 77–78 cytokine receptor 75 DUX4-rearranged ALL 76 Early T-cell precursor (ETP) ALL 79

ETV6::RUNX1 ETV6::RUNX1-like 73

H3K27ac HiChIP high hyperdiploid ALL 69–71 hyperdiploid ALL 71–72 IKZF1N159Y 78–79 immature T-ALL 79 intrachromosomal amplification of

255

256

8–9

404–406

see also ALL

68–69, 70, 72, 79

T-ALL

74–75

chromosome 21 (iAMP21) 72–73

kinase signaling

KMT2A-rearranged ALL MEF2D-rearranged ALL NUTM1-rearranged ALL

PAX5 P80R PAX5alt 77 PAX5-driven ALL 77 Ph-like ALL 74–75 T/M MPAL TAL1 80 T-ALL subtypes 68, 78–80

TCF3::HLF 73 TCF3::PBX1 TCF3-rearranged ALL 73 TLX1 79–80 TLX3 79–80 ZNF384-rearranged leukemia 76

acute myeloid leukemia (AML), 33–50; see

also AML

activated signaling

c-KIT 41 FLT3 (FMS-like tyrosine

kinase3)

chromatin modifiers 46

ASXL1 (Additional Sex Combs

Like-1)

KTM2A 46 cohesion complex gene 44 cytogenetic abnormalities 36–38

acute promyelocytic leukemia 37

chromosomal translocations 38

core-binding factor (CBF)

leukemias 36–37 KMT2A gene 37–38 numerical chromosomal

abnormalities 38

DNA methylation 44–45

DNMT3A EZH2 45

77–78

40–41

44–45

IDH1 IDH2

TET2

genetic aberrations

driver gene mutations molecular 39–40

NPM1 40 germline predisposition 46–48 molecular markers 33 MRD monitoring myeloid transcription factors 41–42

CEBPA (CCAAT/enhancer-binding

protein α)

RUNX1 spliceosome genes 43–44 therapies 48–49 tumor suppressors 42–43

BCOR (BCL6 corepressor)

TP53 (Tumor protein 53) 42–43

WT1 (Wilms tumor 1) 43

acute promyelocytic leukemia 37 adaptive immune system 300 adeno-associated virus gene

transfer

adenosine deaminase (ADA)

deficiency adenoviral gene transfer adenovirus 324 adhesion molecules, blood group

antigens 291–292 ADP receptor defects 257 adverse drug reactions (ADR) 346 Africa, SCD 191, 194 African siderosis 184–185 agonist receptor defects 257 ALL subtypes 349 ALL, see acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell

transplantation (HCT) 94–95, 398

33–36, 39–40

39–40

48–49

41–42

333–334

327–328

332–333

本书版权归John Wiley & Sons Inc.所有

413

414 Index

https://t.me/med1917

allografting, GvL 404 allorecognition

52–53, 56–59, 61, 64–65

AML

AML with BCR::ABL1 fusion AML with CBFB::MYH11 fusion AML with CEBPA mutation AML with DEK::NUP214 fusion AML with FUS::ERG AML with KAT6A::CREBBP AML with KMT2A rearrangement AML with MECOM rearrangement AML with MNX1::ETV6 AML with NPM1 mutation AML with NPM1::MLF1 AML with NUP98 rearrangement AML with RBM15::MRTFA fusion AML with RUNX1::RUNX1T1 fusion AML with RUNX1T3(CBFA2T3)::

AML, genetic alterations

mutated genes 61–62 AML post cytotoxic therapy 58 AML risk classification 53 amplification and mismatch detection (AMD),

anaplastic large cell lymphomas

anemia 14 anemia of chronic disease

bone marrow studies 170

cytokines 172

diagnosis 169–170

erythrocyte lifespan

erythropoiesis 170–172

erythropoietin resistance 172

hepcidin–ferroportin interaction 171

hypoferremia

iron absorption 172

iron parameters 169

iron restriction 170–172

pathogenesis 170–172

serum ferritin 169–170

treatment 172–173 anemia of inflammation, see anemia of

Anion-exchanger protein 1 (AE1) 285–289

C-terminal cytoplasmic domain, AE1

deficiencies, AE1 289

mutations, AE1

nitric oxide export, AE1 287–289

N-terminal cytoplasmic domain,

transmembrane segment, AE1 285–286 antenatal diagnosis, hemophilia 225–226 antibody Fc receptor 306–307 anti-CD20monoclonal antibody 314 antigen expression 268 antigen recognition, T-cells 303 antigenic targets, ITP 312

398–399

GLIS2

hemophilia

(ALCL)

chronic disease

AE1 286–287

220

121–122

169–172

289

169–174

172

286

antiplatelet antibodies, ITP antithrombin antithrombin deficiency antithrombotic therapy, oral

cardiovascular diseases (CVDs) clopidogrel, CYP2C19 variants coumarins, CYP2C9 variants coumarins, VKORC1 variants

warfarin APC APL with PML::RARA fusion aplastic anemia (AA) ASXL1 (Additional Sex Combs Like-1) ATP receptor defects atransferrinemia autoimmune hematological

autoreactivity

B-cells 300–301

diet 308

environmental factors 308

environmental toxins 308

epitope spread

genetic factors 305–307

Graves’ disease

Hashimotos thyroiditis 305

hormones 308

human studies 307–309

immune system 299–305

immune thrombocytopenia

205, 207

354

202, 206–207

185

disorders

antibody Fc receptor 306–307 cytokine gene polymorphisms 306

adaptive immune system antigen recognition, T-cells 303 autoimmunity, beneficial

effects autoreactive T-cells B-cells 300–301 cytokines, immune response 301 innate immune system 299–300 major histocompatibility complex soluble molecules 301 T regulatory cells (Tregs) 303–304 T-cell activation 303 T-cell tolerance 302–303 T-cells 300–303 TCR signaling 303 Th1 response, cytokine profile 301–302 Th2 response, cytokine profile

301–302 tolerance 302–304

(ITP) 309–313 antigenic targets 312 antiplatelet antibodies 310–312 chronic refractory ITP 312–313 clinical features 310 diagnosis 310–312 epitopes 312 etiology 310

299–320

307

308–309

305

304–305

310–312

207

353–356

353

355–356

354

354–355

56–57

145–148, 150

257

300

303

301

pathogenesis

treatment infections inflammatory bowel disease (IBD) mouse models multiple sclerosis (MS) myasthenia gravis psoriasis rheumatoid arthritis Sjögrens syndrome stress

308 systemic lupus erythematosus (SLE) targeted therapies

anti-CD20monoclonal antibody Avatrombopag B-cell inhibitors Bruton tyrosine kinase (BTK)

inhibitors Campath-1H 313–314 complement inhibitors 316 costimulatory blockage 314–315 Eltrombopag Fostamatinib 316 Helicobacter pylori eradication 314–315 neonatal Fc receptor (FcRn)

blockade novel immunomodulatory agents 316 Romiplostim 315 thrombopoietin receptor agonists

(TPO-RAs)

T-cells 300–302 tissue damage 308–309 Type 1 diabetes 305

UV radiation 308 autoimmunity, beneficial effects autoreactive T-cells 303 autoreactivity 307 autosomal dominant segregation,

VWD

autosomal recessive segregation,

VWD

Avatrombopag 315

β-globin chain variants 11 β-globin gene transcription 9 β thalassemia 9–11

β-globin chain variants 11

β-globin gene transcription 9

mRNA abnormal processing 9–10

mRNA abnormal transcription 10

rare forms 11

therapies 14–15

anemia 14 environmental mechanisms 14 gene editing 15 gene therapy 15 genetic modifiers 14 pharmacological options 14–15 phenotypic diversity 14

311

312–313

308

307

305

313–316

315

316

315

316

315–316

304–305

236

305

314

本书版权归John Wiley & Sons Inc.所有

Index 415

https://t.me/med1917

B-ALL subtypes, ALL 68–69, 70, 72, 79 basic helix-loop-helix (bHLH) T-ALL B-cell aplasia, CAR-T cell therapy B-cell inhibitors B-cell lymphomas B-cell precursor, ALL B-cell receptor signaling, CLL B-cells, autoimmune disorders B-cells, immune system

BCL11B-driven ALL BCL2 gene family

BCOR (BCL6 corepressor)

BCR::ABL1 oncogene BCR::ABL1 positive ALL BCR::ABL1 signaling pathways

Bernard–Soulier syndrome (BSS) biodirectional interconversion,

bleeding disorders blood cell alloantigens

antigen expression 268 hemolytic disease of the fetus and newborn

fetal anemia HDFN treatment 283 immunization 282 K immunogenicity 283 Kell 282–283 RhD immunogenicity RH genes 281 Rh proteins 282

Rh system 281 HNA antigen systems HPA immunogenicity 276 major histocompatibility complex

DNA microarray genotyping

HLA antigens 268–271

HLA class I genes 269–270

HLA class II genes 269–270

HLA gene polymorphism 271

HNA allele frequency 279

HNA allograft rejection 280

HNA detection methods 279

HPA allele frequencies 273

HPA alloimmunization 274–275

long-read sequencing

molecular detection methods

molecular typing 271

next generation sequencing 272

PCR-SSP 271

platelet glycoproteins 275

platelet-specific antigens

reverse PCR-SSOP 271–272

sequencing-based typing 272

third-generation sequencing 272 neonatal alloimmune neutropenia 280

316

121, 375–377

78–79

131–132

85, 92

CSC

359–360

251–252, 253

267–284

280–283

(HDFN)

283

268–275

(MHC)

273–274

(HPA) 273–274

300–301

74–75

282

278–279

272

383

130–131

300–301

85–86

252–254

272–273

neonatal alloimmune

thrombocytopenia platelet refractoriness post-transfusion purpura (PTP) red blood cell antigens Transfusion Related Acute Lung Injury

280

(TRALI)

blood coagulation

antithrombin APC factor V FVa

202, 204

FVIIIa

202

FXa initiation management, thrombophilia propagation protein C regulation 202–206 severe thrombophilia 212 thrombomodulin (TM) 203 thrombophilia, severe 212 venous thromboembolism

antithrombin deficiency 207 APC resistance 206–207 factor V gene mutations protein C deficiency 207–208 protein S deficiency 209–210 prothrombin mutations 210–211 susceptibilities, VTE 211–212

blood group antigens

adhesion molecules 291–292 Anion-exchanger protein 1

C-terminal cytoplasmic

deficiencies, AE1 289 mutations, AE1 289 nitric oxide export N-terminal cytoplasmic

transmembrane segment 285–286 functions, diverse 293 Duffy blood group 292 glycophorins C and D (GPC/

Kidd blood group 292–293 rhesus (Rh) proteins 289–290

bone marrow egress, HSCs bone marrow failure 145–168

associated conditions bone marrow failure (BMF)

aplastic anemia (AA) 145–148, 150

clonal disorders 152

metabolism, red cells 149

paroxysmal nocturnal hemoglobinuria

205, 207

202

205

204

202

203–206

(VTE)

206–213

285–289

(AE1)

domain

286

286–287

domain

GPD) 290–291

syndromes 145–152

(PNH) 148–152

276–279

275–277

275

280

201–216

212–213

206–207

285–298

287–289

145

somatic mutations, AA

enzyme deficiencies, red cells

glucose 6-phosphate dehydrogenase

deficiency (G6PD)

Pyrimidine 5’-nucleotidase

deficiency

pyruvate kinase (PK) deficiency

162–163 GPI-protein structure inherited BMF syndromes

Diamond-Blackfan anemia

(DBA)

dyskeratosis congenita (DKC) Fanconi anemia (FA) telomere biology disorders

(TBD) inherited GPI deficiency (IGD)

bone marrow failure (BMF)

syndromes aplastic anemia (AA) 145–148, 150 clonal disorders 152 metabolism, red cells paroxysmal nocturnal hemoglobinuria

(PNH) somatic mutations, AA 150

bone marrow niche, CSC targeted

therapy

bone marrow microenvironment,

bone marrow studies, anemia of chronic

disease

British Committee for Standards in

Haematology (BSCH) diagnostic

criteria

British Society for Haematology (BSH)

diagnostic criteria

Bruton tyrosine kinase (BTK) inhibitors 316 Burkitt lymphoma (BL) 115–116

CALR mutations, MPNs Campath-1H 313–314 cancer stem cells (CSC) 359–368

biodirectional interconversion 359–360 cell of origin 360 leukemia-initiating cells 359 leukemic stem cells (LSCs) 359, 361,

363, 365 myeloid leukemia (AML) 359 pre-leukemic stem cells 360–361 targeted therapies 361–365

bone marrow niche, targeting 363–364 cell surface antigens, targeting 361–362 CSC self-renewal, targeting 362 CSC survival, targeting 362–363 epigenetic modifiers, targeting 364–365 LSC dormancy, targeting 363

tumor-initiating cells (TICs) 359

cardiovascular diseases (CVDs) 353 carrier testing, hemophilia 224–225

165–166

158–160

156–158

145–152

148–152

363–364

142–143

170

101

150

160–166

163–165

153

153–160

156–158

153–156

152–153

149

101

106–107

本书版权归John Wiley & Sons Inc.所有

416 Index

https://t.me/med1917

CAR-T-cell exhaustion 381 CAR-T cell manufacturing

cell expansion cell isolation construct integration

CAR-T cell therapy

acute lymphoblastic leukemia

(ALL) areas for improvement B-cell lymphomas CAR-T cell manufacturing

cell expansion cell isolation construct integration

CAR-T resistance, sources

CAR-T-cell exhaustion epitope shedding

chronic lymphocytic leukemia

(CLL) extracellular single-chain variable fragment

(scFv) FDA-approved CAR-T cell products 380 generations, CAR-T cells 370 hinge domain history 369 intracellular co-stimulatory domains 372 failures 370 multiple myeloma (MM) 378–379 successes toxicities 382–384

B-cell aplasia 383 coagulopathy 384 cytokine release syndrome

(CRS)

cytopenias 383 hypogammaglobulinemia 383 immune effector cell-associated

neurotoxicity syndrome

(ICANS)

infections 383 transmembrane domain 371 tumor microenvironment

(TME) cytokine signaling, TME 384–385 structure 385–386 therapeutic approaches 386 treatment strategies

CAR-T resistance, sources 379–382

CAR-T-cell exhaustion

epitope shedding 381–382 CDX2/UBTF ALL 77–78 c-KIT 41 CEBPA (CCAAT/enhancer-binding

protein α) 42 cell-cycle-active drugs 28 cell cycle control, hematopoiesis 20 cell-extrinsic regulators,

hematopoiesis 21–25

373–374

372–373

374–375

372–373

377–378

370–371

371

370

382–383

383

384–387

372–374

373

369–396

370

375–377

372–374

373–374

373

379–382

381

381–382

387

381

cell of origin, CSC cell signaling genes

AML, mutated genes AML with CEBPA mutation AML with NPM1 mutation DEBPA FLT3

ICC 2022 classification

NPM1 TP53

WHO 2022 classification

cell surface antigens, CSC targeted

therapy

cellular compartment model, stem

cells Chédiak–Higashi syndrome chemokine receptors childhood ALL therapy

ALL subtypes 349 drug resistance, relapsed ALL 352–353 G6PD deficiency 348–350 germline genetic variants 349

NT5C2 variants NUDT15 variants 350–352 PRPS1 variants 353

Rasburicase 348–350 relapsed ALL, drug resistance TCF3-HLF ALL therapy 353 thioguanine (TG) 350 thiopurine antimetabolites mercaptopurine

(MP)

thiopurine resistance thiopurine therapy 350–352 TPMT variations 350–351 tumor lysis syndrome (TLS) 348

chorionic villus sampling (CVS),

hemophilia chromatin modifiers, AML 46

ASXL1 (Additional Sex Combs Like-1) 46 KTM2A

chromosomal translocations 38, 55 chromosome 1q gain, MM 142 chromosome abnormalities, CLL 129 chronic eosinophilic leukemia (CEL) 109 chronic GvHD (cGvHD) 405–407 chronic lymphocytic leukemia/small

lymphocytic lymphoma (CLL/

SLL)

B-cell receptor signaling 130–131 BCL2 gene family CAR-T cell therapy 377–378 chromosome abnormalities death mediators 132 diffuse large B-cell lymphoma subtype

(DLBCL-RT) 134–135

DLBCL 130, 134–135 environmental factors 128 epidemiology 128

360

60–65

61–62

62–65

361–362

18–19

259

347–353

352

352–353

350

352–353

226

120–121, 127–136

131–132

129

epigenetic factors genetic factors IGHV mutations impaired immunity microenvironment microRNA molecular biology pro-apoptotic BH3-only proteins prognostic features pro-survival BCL2-like proteins Richter transformation (RT) somatic mutations

chronic myeloid leukemia (CML)

allogeneic hematopoietic stem cell

transplantation (HCT)

BCR::ABL1 oncogene BCR::ABL1 signaling pathways

clinical presentation epidemiology 83 molecular biology 85–86 Philadelphia chromosome 85, 95–96 pregnancy prognostic models 84–85 therapy 86–95

CML-AP 95 CML-BP dose schedules 93 failure 90 frontline CML therapy 87–88, 93 post-TKI resistance resistance 89–90 response 89 selection 88 side effects 90–92 toxicities treatment endpoints 88–89

chronic neutrophoic leukemia

(CNL) chronic refractory ITP classification systems, myeloid

malignancies clinical features, hemophilia 217–218 clinical implications, myeloid

malignancies 55 clinical use, stem cells 27–31

cell-cycle-active drugs 28 exvivo expansion 29 FACS 28 isolation 28–29 magnetic bead columns 28–29 markers, primitive HSCs 28 mobilization 27–28

CLL/SLL, see chronic lymphocytic leukemia/

small lymphocytic lymphoma

(CLL/SLL) clonal cytopenia of undetermined significance

(CCUS) 52 clonal deletion, HCT 400–401

130

128

128–129

133–134

132–133

130

128–130

132

133

132

134–135

129–130

83–98

94–95

85, 92

85–86

83–84

90–92

89–90, 93

108–109

312–313

本书版权归John Wiley & Sons Inc.所有

Index 417

https://t.me/med1917

clonal disorders 152 clonal hematopoiesis of indeterminate

potential (CHIP) clopidogrel, CYP2C19 variants CML, see chronic myeloid leukemia (CML) CML-AP CML-BP CNL diagnostic criteria, MPNs coagulopathy, CAR-T cell therapy coagulation, blood

cobblestone area-forming cells

cohesion complex 60 cohesion complex gene collagen receptor defects 255–256 colony-forming units, spleen (CFU-S) 18 competitive repopulation assay 30–31 complement inhibitors 316 conformation-sensitive gel electrophoresis

copy number variants (CNVs) 345–346 core-binding factor (CBF) leukemias 36–37 costimulatory blockage 314–315 coumarins, CYP2C9 variants coumarins, VKORC1 variants 354–355 CSC, see cancer stem cells (CSC) CSC self-renewal, CSC targeted therapy 362 CSC survival, CSC targeted therapy 362–363 C-terminal cytoplasmic domain, AE1 286 Cyclin D dysregulation 140 Cyclin D genes 139 CYP2C9 variants, coumarins 354 cytogenetic abnormalities, AML 36–38

antithrombin APC

202

205

factor V FVa

202, 204

FVIIIa

204

202

FXa initiation, blood coagulation management, thrombophilia propagation, blood coagulation protein C regulation, blood coagulation 202–206 severe thrombophilia 212 thrombomodulin (TM) 203 thrombophilia, severe venous thromboembolism

acute promyelocytic leukemia 37 chromosomal translocations 38

203–206

206–213

(VTE)

antithrombin deficiency 207 APC resistance 206–207 factor V gene mutations protein C deficiency 207–208 protein S deficiency 209–210 prothrombin mutations 210–211 susceptibilities, VTE

(CAFCs)

(CSGE)

220

51–52

355–356

108

384

201–216

205, 207

202

212–213

202

212

206–207

211–212

18–19

354

core-binding factor (CBF) leukemias

36–37 KMT2A gene numerical chromosomal abnormalities

cytogenetic abnormalities, MM cytogenetic analysis, myeloid malignancies

cytogenetic techniques, lymphonas cytokine gene polymorphisms cytokine receptor, ALL cytokine release syndrome (CRS), CAR-T cell

cytokine signaling, TME cytokine storm, GvHD cytokines cytokines, anemia of chronic disease cytokines, immune response cytopenias, CAR-T cell therapy cytoskeletal defects 260–261

death mediators DEBPA 61 deficiencies, AE1 Del(1p32) 142 Del(13q) 141 deletion of 17(p) 142 denaturing gradient gel electrophoresis

dense (δ) granule defects 258 desmopressin 243–244 developmental model, MM 141 diagnostic criteria, MM Diamond-Blackfan anemia (DBA)

diet, autoimmune disorders diffuse large B-cell lymphoma, not otherwise

diffuse large B-cell lymphoma subtype

DLBCL, 130, 134–135; see also diffuse large

DNA methylation 44–45, 60

DNMT3A 44–45 EZH2,45

IDH1 45 IDH2 45

TET2

DNA microarray genotyping 272–273 DNMT3A donor lymphocyte infusions (DLI),

dose schedules, CML therapy 93 driver gene mutations 39–40 drug-related phenotypes 347 drug resistance, relapsed ALL 352–353

37–38

53–54, 56–58, 64

382–383

therapy

384–385

405–406

21–25

301

132

289

(DGGE)

220

138

158–160

308

specified (DLBCL, NOS)

(DLBCL-RT)

B-cell lymphoma, not otherwise

specified (DLBCL, NOS) and diffuse

large B-cell lymphoma subtype

(DLBCL-RT)

44–45

GvL 402–404

134–135

139

114

306

172

383

116–117

Duffy blood group DUX4-rearranged ALL dyskeratosis congenita (DKC)

EAHAD Coagulation Factor Variant

Databases Early T-cell precursor (ETP) ALL Eltrombopag engraftment, HSCs environmental factors, autoimmune

disorders environmental factors, CLL environmental toxins, autoimmune

disorders enzyme deficiencies, red cells

glucose 6-phosphate dehydrogenase

deficiency (G6PD)

Pyrimidine 5’-nucleotidase

deficiency

pyruvate kinase (PK) deficiency

162–163 eosinophilia epidemiology

128

CLL CML 83 SCD

189, 191–192 epidrugs 346 epigenetic factors, CLL 130 epigenetic modifiers, CSC targeted

therapy epigenetic regulators 59 epigenetic variations,

pharmacogenomics epitope shedding 381–382 epitope spread, autoimmune

disorders epitopes, ITP 312 erythrocyte lifespan 172 erythropoiesis erythropoietin resistance 172 essential thrombocythemia 100–101 ET, MPNs 105–108 ethnic groups, pharmacogenomics 347 etiology, ITP 310

ETV6::RUNX1 73 ETV6::RUNX1-like 73 exvivo expansion 29

extracellular single-chain variable fragment

(scFv) 370–371 EZH2 45

F8 gene 219–220 F9 gene 222

FACS 28 factor IX 217–218, 221–222, 224, 226, 228 factor V 205–207 factor VII 221, 228 factor VIII 217–219, 221, 223–224, 226–229

292

156–158

221

315

25–27

308

128

308

160–166

163–165

165–166

104

364–365

346

308–309

23, 170–172

本书版权归John Wiley & Sons Inc.所有

418 Index

https://t.me/med1917

factor X 222 Fanconi anemia (FA) Ferroportin disease fetal anemia

283

fetal hemoglobin, SCD

153–156

184

196–197

FLT3 (FMS-like tyrosine kinase 3)

40–41, 61

fluorescence in-situ hybridization

(FISH)

113–114 follicular lymphoma (FL) Fostamatinib

316 frontline CML therapy function, hemoglobin

globin gene loci globin gene transcription globin RNA

4–5

globin switching

functional analysis, stem cells

113, 118–119

87–88, 93

2–6

3–4

5–6

29–31 competitive repopulation assay invitro assays

29–30

invivo assays 30–31

FVa 202, 204 FVIIIa 204 FXa

202

G6PD deficiency

348–350 gene editing 15 gene therapy 15, 321–342

adeno-associated virus gene

transfer

333–334 adenoviral gene transfer 332–333 adenovirus 324 genetic immunotherapy

334–337 helper dependent adenovirus 324 hematological malignancies 335 hematopoietic stem cells (HSCs)

322, 327 herpes simplex virus gene transfer herpes virus 324 HIV retrovirus 325 lentiviral gene transfer 330–332 lentivirus 324–325 oncoretrovirus 324–329

adenosine deaminase (ADA)

deficiency 327–328

immunodeficiencies,

inherited 328–329

long terminal repeats (LTRs) 324 lysosomal storage disorders

(LSDs) 329

MDR-1 327 Moloney murine leukemia virus

(MMLV) 324

neomycin phosphotransferase

(neo

) 326

P-glycoprotein 237 replication-competent retrovirus

(RCR) 324

30–31

334

severe combined immunodeficiency

(SCID) of ADA (ADA-SCID) 328–329

329

Tecartus

329

Yescarta pox viruses resistance immunotherapy safety suicide gene therapy viral vectors

gene therapy, hemophilia gene transfer

324

336

337–339

323–324

228–229

321–342

adeno-associated virus gene

333–334

transfer adenoviral gene transfer adenovirus

324 genetic immunotherapy helper dependent adenovirus hematological malignancies

332–333

334–337

324

335 hematopoietic stem cells (HSCs) 322, 327 herpes simplex virus gene transfer

334 herpes virus 324 HIV retrovirus 325 lentiviral gene transfer 330–332 lentivirus

324–325

oncoretrovirus 324–329

adenosine deaminase (ADA)

deficiency

327–328

immunodeficiencies,

inherited

328–329 long terminal repeats (LTRs) 324 lysosomal storage disorders (LSDs) 329 MDR-1 327 Moloney murine leukemia virus

(MMLV)

neomycin phosphotransferase (neo

324

P-glycoprotein 237 replication-competent retrovirus

(RCR)

324

severe combined immunodeficiency

(SCID) of ADA

(ADA-SCID) 328–329 Tecartus 329 Yescarta 329

pox viruses 324 resistance immunotherapy 336 safety 337–339 suicide gene therapy 337–339 viral vectors 323–324

genetic aberrations, AML 33–36, 39–40

driver gene mutations 39–40 molecular 39–40 NPM1 40

genetic defects, VWD 235–243

autosomal dominant segregation 236 autosomal recessive segregation 236 Type 1 VWD 237–239, 246 Type 2 VWD 239–243

) 326

Type 2A VWD Type 2B VWD Type 2M VWD Type 2N VWD Type 3 VWD

genetic determinants, SCD

239–241, 246

241, 246

241–243, 246

243, 246

242–243, 246

193–196

genetic factors, autoimmune

disorders antibody Fc receptor cytokine gene polymorphisms

genetic factors, CLL genetic immunotherapy genetic modifiers genetic risk models, SCD genetic techniques, lymphomas

305–307

306–307

306

128

334–337

198–199

113–115

germline genetic variants, childhood ALL

therapy

349 germline JAK2 mutations, MPNs germline predisposition, AML

104

46–48 giant platelet syndromes 260–261 Glanzmann thrombasthenia (GT) 256–257 globin gene loci 3–4

JAK2 exon12mutations, MPNs 103–104

globin genes

7–11

α thalassemias 7–9

Thalassemia 7

Thalassemia 7–8 mutations that cause 9 variants

8–9

β thalassemia 9–11

β-globin chain variants 11 β-globin gene transcription 9

mRNA abnormal processing

9–10 mRNA abnormal transcription 10 rare forms 11

δβ Thalassemia 11 hereditary persistence of fetal hemoglobin

(HPFH)

11 globin gene transcription 5 globin RNA 4–5 globin switching 5–6 glycophorins C and D (GPC/GPD) 290–291 glucose 6-phosphate dehydrogenase

deficiency (G6PD) 163–165 Glycosylation defects 261 GPI-protein structure 153 GPIbα

253–254 GPIbα monoallelic mutations 254 GPIbβ monoallelic mutations

254 GPlb-V-IX complex 253 GPV 254 GPVI

255–256

graft-versus-host (GvHD), HCT 402–410

acute GvHD 404–406 chronic GvHD (cGvHD) 405–407 cytokine storm 405–406 immunological targets 402 NK-cells 410

本书版权归John Wiley & Sons Inc.所有

preventions 408–409

https://t.me/med1917

T-cell trafficking treatment

graft-versus-leukemia (GvL), HCT

402–405, 407–410 allografting donor lymphocyte infusions

(DLI) immunological targets selective tumor-specific T-cells

granulocyte macrophage colony-stimulating

factor (GM-CSF)

granulopoiesis Graves’ disease gray platelet syndrome Griscelli syndrome

H3K27ac HiChIP haplotype map haplotypes 345 Hashimotos thyroiditis 305 HbA production, SCD 195–196 HbF, SCD, SCD HbS allele (HbAS), SCD 187, 191, 194 HDFN treatment 283 Helicobacter pylori eradication 314–315 helper dependent adenovirus 324 hematological malignancies hematopoiesis, defined 17 hematopoiesis, molecular regulation

20–25 cell cycle control cell-extrinsic regulators 21–25 chemokine receptors 25 cytonkines 21–25 hematopoietic control factors lineage determinations 20–21 protein serine–threonine kinase

receptors receptor, tyrosine kinases 22 self-renewal 20–21 transcription factors 21 tumor necrosis factor receptor (TNFR) 25 Type I cytokine receptors 21–22 Type II cytokine receptors 22

hematopoietic cell transplantation (HCT) hematopoietic control factors 23–24 hematopoietic ontogeny hematopoietic progenitor cells (HPCs) 397 hematopoietic stem cells (HSCs) 322, 327 hemochromatosis 184 hemoglobin

function 2–6 structure 2–6

globin gene loci 3–4 globin gene transcription 5 globin RNA 4–5

406

408–409

404

402–404

402

409–410

404

23–24

305

258

259

345

187, 192–198

335

23–24

22–25

25–26

globin switching

hemolytic disease of the fetus and newborn

(HDFN) fetal anemia HDFN treatment immunization K immunogenicity Kell

282–283 RH genes Rh proteins Rh system RhD immunogenicity

hemophilia

amplification and mismatch detection

antenatal diagnosis carrier testing chorionic villus sampling (CVS) clinical features 217–218 conformation-sensitive gel electrophoresis

denaturing gradient gel electrophoresis

EAHAD Coagulation Factor Variant

F8 gene 219–220 F9 gene

factor IX 217–218, 221–222, 224, 226, 228 factor VII 221, 228 factor VIII 217–219, 221, 223–224,

factor X gene therapy 228–229 hemophilia A 219–221 hemophilia B 221–222 hemorrhagic manifestations high-resolution melting analysis

inheritance 218–219, 225 inhibitor formation intron 22inversion 220 non-factor therapies 228 plasma-derived, von Willebrand factor

recombinant factors 226–228 variants 221, 223

hemophilia A 219–221 hemophilia B 221–222 hemopoietic cell transplantation

allogeneic HCT 398 allorecognition clonal deletion 400–401 graft-versus-host (GvHD) 402–410

281

217–230

(AMD)

(CSGE)

(DGGE)

Databases

222

226–229

222

(HRM)

(VWF) 224

(HCT) 397–412

acute GvHD 404–406 chronic GvHD (cGvHD) 405–407 cytokine storm 405–406 immunological targets 402

5–6

280–283

283

282

283

282

220

225–226

224–225

226

220

221

218

220

222–224

398–399

Index 419

410

NK-cells preventions T-cell trafficking treatment

graft-versus-leukemia (GvL)

407–410 allografting donor lymphocyte infusions

(DLI) immunological targets selective tumor-specific T-cells

hematopoietic progenitor cells

(HPCs)

immunosuppression, HSCT major histocompatibility complex

(MHC)

peripheral regulation separating GvHD and GvL 407–410 tolerance 400–401

hemorrhagic manifestations,

hemophilia

hemostasis 231–232 hepcidin 179–181 hepcidin–ferroportin interaction 171 hereditary persistence of fetal hemoglobin

(HPFH)

Hermansky-Pudlak syndrome 258 herpes simplex virus gene transfer 334 herpes virus HFE-related hemochromatosis 182–183 high hyperdiploid ALL 69–71 high-resolution melting analysis (HRM) 220 hinge domain, CAR-T cells 371 histone modification HIV retrovirus 325 HLA antigens 268–271 HLA class I genes 269–270 HLA class II genes HLA gene polymorphism 271 HNA allele frequency 279 HNA allograft rejection 280 HNA antigen systems 278–279 HNA detection methods 279 Hodgkin lymphoma 113 homing, HSCs 25–27 hormones, autoimmune disorders 308 HPA allele frequencies 273 HPA alloimmunization 274–275 HPA immunogenicity 276 HPFH, see hereditary persistence of fetal

hemoglobin (HPFH)

HSCs, see stem cells human genome variation 344–347

adverse drug reactions (ADR) 346 copy number variants (CNVs) 345–346 drug-related phenotypes 347 epidrugs 346

408–409

406

408–409

402–405,

404

402–404

402

409–410

404

397

408

398

401

218

324

269–270

本书版权归John Wiley & Sons Inc.所有

420 Index

https://t.me/med1917

human genome variation (Continued)

epigenetic variations 346 ethnic groups haplotype map haplotypes immunopharmacogenomics linkage disequilibrium single-nucleotide variants somatic variations

human studies, autoimmune

hyperdiploid ALL hyperdiploid, MM hypoferremia hypogammaglobulinemia, CAR-T cell

ICC 2022 classification, myeloid

IDH1 45 IDH2 45

IgH translocations 139–140 IGHV mutations, CLL IKZF1N159Y 78–79 immature T-ALL 79 immune effector cell-associated neurotoxicity

immune system 299–305

adaptive immune system 300 antigen recognition, T-cells 303 autoimmunity, beneficial effects autoreactive T-cells 303 B-cells 300–301 cytokines, immune response 301 innate immune system major histocompatibility complex 301 soluble molecules 301 T regulatory cells (Tregs) 303–304 T-cell activation T-cell tolerance 302–303 T-cells 300–303 TCR signaling 303 Th1 response, cytokine profile 301–302 Th2 response, cytokine profile 301–302 tolerance 302–304

immune thrombocytopenia (ITP) 309–313

antigenic targets 312 antiplatelet antibodies 310–312 chronic refractory ITP 312–313 clinical features 310 diagnosis 310–312 epitopes 312 etiology 310 pathogenesis 311 treatment 312–313

immunization, HDFN 282

347

345

346

345

346

disorders

therapy

malignancies

syndrome (ICANS), CAR-T cell therapy

307–309

71–72

139

169–172

383

62–65

128–129

383

304–305

299–300

303

immunodeficiencies, inherited immunological targets, GvHD immunological targets, GvL immunopharmacogenomics immunosuppression, HSCT impaired immunity, CLL invitro assays invitro colony-forming cells (CFCs) invivo assays infections

autoimmune disorders

CAR-T cell therapy inflammatory bowel disease (IBD) inheritance, hemophilia inherited BMF syndromes

Diamond-Blackfan anemia

dyskeratosis congenita (DKC)

Fanconi anemia (FA) 153–156

telomere biology disorders

inherited GPI deficiency (IGD) 152–153 inhibitor formation, hemophilia 222–224 initiating cells (ICs) 18 initiation, blood coagulation innate immune system 299–300 International Myeloma Working Group 138 International Prognostic Scoring System-

intestinal iron transport intracellular co-stimulatory domains, CAR-T

intracellular signaling pathways, defects 258 intrachromosomal amplification of

intrinsic coagulation, VWD 232 intron 22inversion, hemophilia 220 iron absorption, anemia of chronic

iron-deficiency disorders 182 iron disorders 181–185

aceruloplasminemia

African siderosis 184–185

atransferrinemia 185

Ferroportin disease 184

hemochromatosis 184

HFE-related hemochromatosis 182–183

iron distribution, abnormal 185

iron overload disorders 182

iron-deficiency disorders 182

non-HFE-related

iron distribution, abnormal 185 iron homeostasis 178–181 iron metabolism 175–186

hepcidin 179–181

intestinal iron transport 176

29–30

30–31

158–160

(DBA)

(TBD)

156–158

Molecular (IPSS-M)

372

cells

chromosome 21 (iAMP21) 72–73

disease

172

hemochromatosis 183–184

328–329

402

346

408

133–134

308

383

305

218–219, 225

153–160

156–158

202

176

185

iron disorders

aceruloplasminemia African siderosis atransferrinemia Ferroportin disease hemochromatosis HFE-related

hemochromatosis iron-deficiency disorders iron distribution, abnormal iron overload disorders non-HFE-related

hemochromatosis

iron homeostasis iron storage iron transport regulators, iron transferrin cycle

transport mechanisms, iron 175–178 iron overload disorders iron parameters, anemia of chronic

disease

iron restriction, anemia of chronic

disease iron storage 178–179 iron transport 175–178 isolation, stem cells 28–29

JAK2 germline haplotype, MPNs

104–105

JAK2 mutations, MPNs JAK2 V617F mutation, MPNs 101–103 JAK2 variants, MPNs

JAKs, defined 99 JAK-STAT pathways, MPNs 99–101

K immunogenicity, HDFN karyotypes 113 karyotypic evolution 55 Kell, HDFN 282–283 Kidd blood group kinase signaling 75 KMT2A gene 37–38, 46 KMT2A-rearranged ALL 74

lentiviral gene transfer 330–332 lentivirus 324–325 leukemia-initiating cells 359 leukemic stem cells (LSCs) 359, 361, 363,

365 life expectancy, SCD 192 lineage commitment models 19–20 lineage determinations,

hematopoiesis 20–21 linkage disequilibrium,

pharmacogenomics 345 long terminal repeats (LTRs) 324

181–185

185 184–185 185

184

182–183

182

185

182

183–184

178–181

178–179

175–178

179

177–178

182

169

170–172

104

283

292–293

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Index 421

https://t.me/med1917

long-read sequencing, MHC 272 long-term culture-initiating cells

(LTC-ICs) LSC dormancy, CSC targeted therapy lymphoma

anaplastic large cell lymphomas

(ALCL)

B-cell lymphomas Burkitt lymphoma (BL) chronic lymphocytic leukemia/small

lymphocytic lymphoma (CLL/

SLL)

cytogenetic techniques diffuse large B-cell lymphoma, not

otherwise specified (DLBCL,

NOS)

fluorescence in-situ hybridization

(FISH)

follicular lymphoma (FL) genetic techniques Hodgkin lymphoma 113 karyotypes 113 lymphoplasmacytic lymphoma (LPL)

119

mantle cell lymphoma marginal zone lymphoma

(MZL)

nodal T-follicular helper (TFH) cell

lymphomas (nTFHLs)

peripheral T-cell lymphomas, not

otherwise specified (PTCL-NOS)

122–123

Reed-Sternberg cell

T-cell lymphomas 123 lymphoplasmacytic lymphoma (LPL) 119 lymphopoiesis 24 lysosomal storage disorders (LSDs)

magnetic bead columns major histocompatibility complex

(MHC) DNA microarray genotyping 272–273 HCT 398 HLA antigens 268–271 HLA class I genes 269–270 HLA class II genes 269–270 HLA gene polymorphism HNA allele frequency 279 HNA allograft rejection HNA detection methods 279 HPA allele frequencies 273 HPA alloimmunization 274–275 immune system 301 long-read sequencing 272 molecular detection methods 273–274 molecular typing 271 next generation sequencing 272 PCR-SSP 271

363

113–126

121–122

121

115–116

120–121

114

116–117

113–114

113, 118–119

113–115

118

119–120

122

113

329

28–29

268–275

271

280

platelet glycoproteins platelet-specific antigens (HPA) reverse PCR-SSOP sequencing-based typing

third-generation sequencing management, SCD management, thrombophilia mantle cell lymphoma marginal zone lymphoma (MZL) markers, primitive HSCs

327

MDR-1

MDS

52, 56, 58–59, 63 MDS cytogenetic abnormalities Medich giant platelet syndrome MEF2D-rearranged ALL metabolism, iron

hepcidin

179–181 intestinal iron transport iron disorders 181–185

aceruloplasminemia 185 African siderosis 184–185 atransferrinemia 185 Ferroportin disease hemochromatosis 184 HFE-related

hemochromatosis iron-deficiency disorders iron distribution, abnormal 185 iron overload disorders 182 non-HFE-related

hemochromatosis

iron homeostasis iron storage 178–179 iron transport 175–178 regulators, iron 179 transferrin cycle

transport mechanisms, iron 175–178 metabolism, red cells 149 MF, MPNs 105–108 microenvironment, CLL microRNA 130

MLL, see KTM2A

MM, see multiple myeloma (MM) mobilization, stem cells 27–28 models, pharmacogenomics 347 molecular biology, CLL 128–130 molecular biology, CML 85–86 molecular detection methods,

MHC 273–274 molecular genetic aberrations molecular markers, AML 33 molecular typing, MHC Moloney murine leukemia virus

(MMLV) 324 mortality, SCD 192 mouse models, autoimmune disorders 307 MPL mutations, MPNs 105–106 MRD monitoring, AML 48–49

275

273–274

271–272

272

193–196

212–213

118

119–120

56 261

175–186

176

184

182–183

182

183–184

178–181

177–178

132–133

39–40

271

mRNA abnormal processing mRNA abnormal transcription multiple myeloma (MM), 137–144;

see also MM bone marrow microenvironment CAR-T cell therapy chromosome 1q gain classification Cyclin D dysregulation Cyclin D genes cytogenetic abnormalities Del(13q) Del(1p32) deletion of 17(p) developmental model diagnostic criteria hyperdiploid IgH translocations 139–140 International Myeloma Working

MYC signaling 141–142 myeloma cell development NFkB family 142 plasma cell development 137–138 progression 140–143 R2-ISS RAS abnormalities 141 revised international staging system

risk stratification secondary abnormalities 140 t(11;14)(q13;q32) 139–140 t(14;16) (q32;q23) 140 t(14;20) (q32;q11) 140 t(4;14) (p16;q32) trisomies 139

multiple sclerosis (MS) 305 multipotent, stem cells 17 mutated genes, AML mutations, AE1 289 myasthenia gravis 305 MYC signaling 141–142 myelodysplastic neoplasms, childhood 63 myeloid leukemia (AML) 359 myeloid malignancies 51–66

AML 52–53, 56–59, 61, 64–65 AML post cytotoxic therapy 58 AML risk classification 53 cell signaling genes 60–65

AML, mutated genes 61–62 AML with CEBPA mutation 62 AML with NPM1 mutation 62 DEBPA 61 FLT3 61 ICC 2022 classification 62–65 NPM1 61 TP53 61 WHO 2022 classification 62–65

141

Group

143

(R-ISS)

143

139

142

139

138

143

140

9–10

142–143

378–379

142

140

139

141

138

138–140

61–62

本书版权归John Wiley & Sons Inc.所有

422 Index

https://t.me/med1917

myeloid malignancies (Continued)

chromosomal translocation 55 classification systems clinical implications

clonal cytopenia of undetermined

significance (CCUS)

clonal hematopoiesis of indeterminate

potential (CHIP) cohesion complex cytogenetic analysis detection methods DNA methylation epigenetic regulators

51–52

53–54, 56–58, 64

54–55

hematopoietic cell transplantation

(HCT) histone modification

International Prognostic Scoring

System-Molecular (IPSS-M) 57 karyotypic evolution

55 MDS 52, 56, 58–59, 63 myelodysplastic neoplasms, childhood 63 myeloid sarcoma 65 somatic mutations

64–65 splicing factors, mutations 58–59 transcription factors 60 treatment 55–58

AML cytogenetic aberrations

56–58 AML with BCR::ABL1 fusion 58 AML with CBFB::MYH11 fusion 57 AML with DEK::NUP214 fusion 57 AML with FUS::ERG 58 AML with KAT6A::CREBBP

58 AML with KMT2A rearrangement 57 AML with MECOM rearrangement 58 AML with MNX1::ETV6 58 AML with NPM1::MLF1

58 AML with NUP98 rearrangement 58 AML with RBM15::MRTFA fusion 57 AML with RUNX1::RUNX1T1

fusion

AML with RUNX1T3

(CBFA2T3)::GLIS2

58 AML, genetic alterations 58 APL with PML::RARA fusion 56–57 MDS cytogenetic abnormalities 56

myeloid sarcoma 65 myeloid transcription factors, AML 41–42

CEBPA (CCAAT/enhancer-binding

protein α) 42

RUNX1 41–42 myeloma cell development 138–140 myeloproliferative neoplasms (MPNs),

99–112; see also MPNs

British Committee for Standards in

Haematology (BSCH) diagnostic criteria 101

British Society for Haematology (BSH)

diagnostic criteria 101

CALR mutations

106–107

chronic eosinophilic leukemia

(CEL)

109

chronic neutrophoic leukemia

108–109

(CNL) CNL diagnostic criteria eosinophilia

104

essential thrombocythemia

105–108

ET germline JAK2 mutations

JAK2 exon12mutations JAK2 germline haplotype JAK2 mutations JAK2 V617F mutation JAK2 variants

104

JAK-STAT pathways

105–108

MF molecular information

108

100–101

104

103–104

104–105

104

101–103

99–101

109–110 MPL mutations 105–106 Philadelphia-negative 101–102 polycythemia vera

100–101 primary myelofibrosis 100–101 PV 106–107 reticulin deposition 108 somatic mutations

106–108

WHO 2022 diagnostic criteria 100

neomycin phosphotransferase (neo

) 326 neonatal alloimmune neutropenia 280 neonatal alloimmune

thrombocytopenia

276–279 neonatal Fc receptor (FcRn) blockade 316 next generation sequencing, MHC 272 NK-cells, GvHD

410 NFkB family 142 nitric oxide export, AE1 287–289 nodal T-follicular helper (TFH) cell

lymphomas (nTFHLs)

non-factor therapies, hemophilia

122

228

non-HFE-related

hemochromatosis

183–184 novel immunomodulatory agents 316 NPM1 40, 61 NT5C2 variants, childhood ALL

therapy 352

N-terminal cytoplasmic domain,

AE1 286–287

NUDT15 variants, childhood ALL

therapy 350–352

numerical chromosomal abnormalities

NUTM1-rearranged ALL 77–78

oncoretrovirus 324–329

adenosine deaminase (ADA)

deficiency 327–328 immunodeficiencies, inherited 328–329 long terminal repeats (LTRs) 324 lysosomal storage disorders (LSDs) 329

MDR-1

327

Moloney murine leukemia virus

(MMLV)

neomycin phosphotransferase (neo

P-glycoprotein

324

237

) 326

replication-competent retrovirus

324

(RCR)

severe combined immunodeficiency (SCID)

of ADA (ADA-SCID)

Tecartus

329

Yescarta

oral antithrombotic therapy

cardiovascular diseases (CVDs) clopidogrel, CYP2C19 variants coumarins, CYP2C9 variants coumarins, VKORC1 variants warfarin

354

328–329

353–356

353

355–356

354

354–355

paroxysmal nocturnal hemoglobinuria

(PNH)

148–152

pathogenesis, anemia of chronic

170–172

disease

pathogenesis, ITP

311

pathology, molecular 1–16

function, hemoglobin 2–6 globin genes 7–11

α thalassemias

7–9

β thalassemia 9–11 δβ Thalassemia 11

hereditary persistence of fetal

hemoglobin (HPFH) 11

phenotypes of thalassemia

12–15

α thalassemia, 12-13 β thalassemias

13–14

therapies 14–15

structure, hemoglobin

2–6 globin gene loci 3–4 globin gene transcription 5 globin RNA 4–5 globin switching

5–6

thalassemia phenotypes 12–15 pathophysiology, SCD 192 PAX5-driven ALL 77 PAX5alt 77 PAX5 P80R 77 PCR-SSP 271 peripheral regulation, HCT 401 peripheral T-cell lymphomas, not otherwise

specified (PTCL-NOS) 122–123

P-glycoprotein

237

pharmacogenomics 343–358

antithrombotic therapy, oral

353–356 cardiovascular diseases (CVDs) 353 clopidogrel, CYP2C19 variants

355–356 coumarins, CYP2C9 variants 354 coumarins, VKORC1 variants 354–355 warfarin 354

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