Myeloid Maturation
myeloblast |
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promyelocyte myelocyte metamyelocyteband |
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neutrophil |
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MATURATION 
Lymphoblast/Myeloblast
Epidemiology of acute leukemia
•2-3% of all malignancies.
•Morbidity: 3-5 per 100 000
•Diagnosis: 75% - in adults, 25% - in children
•In general myelo/lympho = 6:1
•In adults >40 years old = 4:1
•In children: 1:9
•Median age for AML = 60-65 years, for ALL = 10 years
Etiology
•Genetics
•Unstable genome in congenital disorders
•Radiation
•Chemicals
•Viruses (HLTV-1, EBV, HCV, HIV)
•Smoking (AML)
Two-hit model of leukemogenesis
Loss of function of transcription factors needed for differentiation
eg. AML1-ETO CBFb-SMMHC PML-RARa
Gain of function mutations of tyrosine kinases
eg. FLT3, c-KIT mutations
N- and K-RAS mutations
BCR-ABL TEL-PDGFbR
differentia |
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enhanced |
Acute |
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proliferati |
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Leukemia |
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block |
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Clinical presentation
•Anemic syndrome
•Infections and intoxication
•Haemorrhagic syndrome
•Lymphoprolipherative syndrome
•Syndrome of tumor toxicity
•Syndrome of tumor progression
•Leukostasis
Stages of acute leukemia
•Onset
-Systemic inflammatory syndrome (fever, fatigue, intoxication)
-Symptoms associated with supression of normal hemopoiesis (anemia, haemorrhages, infections)
•Remission
•Partial
•Total (≤5% of blasts in bone marrow, normal hemopoiesis, normal general overall health, normal CBC, regression of organomegaly)
•Resistant form (no effect after 2 months of therapy)
•Minimal residual disease (residual population of leukemic cells, detected by highly sensitive methods)
•Relapse (>5% of blasts in bone marrow)
Extramedullar clinical presentation of acute leukemia
•Gum hyperplasia – infiltration of gums with blasts (specific for myeloid leukemia)
•Leukemia cutis – infiltration of the skin with blasts (formation of сyanotic lesions)
•Chloroma – solid extramedullary myeloid tumor composed of myeloblasts
•Involvement of the central nervous system -Meningeal symptoms
-Arterial hypertension -Papilledema -Nystagmus, squinty eyes -Paresthesia
•Leukemic infiltration of the organs: lungs, gut, myocardium
Leukemia cutis and chloroma
Chloroma in Acute Myelogenous Leukemia Christian Sauter, M.D., and Emanuel Jacky, M.D. N Engl J Med 1998; 338:969