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Marist College
Jennifer Finn

HEMATOLOGY#25 -- LEUKEMIAS OF MYELOID CELLS I. Leukemia definition -- purposeless proliferation of a clone of abnormal hematopoietic cells with common characteristics A. unresponsive to cell regulatory mechanisms B. diminished capacity for normal differentiation C. proliferate at expense of normal myeloid or lymphoid cell lines D. suppress or impair normal cell lines E. two main types 1. Acute - predominantly immature clones 2. Chronic - predominantly mature clones II. Incidence A. 4% of all cancers in U.S. B. 50% of acute leukemias arise in children C. AML most common adult form D. CLL uncommon before age of 40 E. CML more common in middle age Percentaqe of cases among leukemias Chronic leukemias CLL 25% CML 22% myelomonacytic: 3% Acute leukemias: ALL 20% AML 20% myelomonablastic 10% III. Etiology of leukemias A. uncontrolled cell division not responsible for rapid increase in tumor mass 1. normal myeloblasts follow fixed developmental sequence and do'not divide after myelocyte stage===>circulate===>die. 2. leukemic cells remain indefinitely capable of cell division -- random release from marrow; may settle in other organs; divide & reenter circulation 3. pathophysiology relates most directly to impact of expanding population of cells a. infiltrate marrow----->aplastic marrow death by hemorrhage or infection b. leukemic cells cause organ dysfunction B. human leukemias occur as effect of environment 1. ionizing radiation exposure 2. after marrow hypoplasia induced by chloramphenicol or benzene 3. treatment with alkylating agents 4. retroviruses a. Human T cell Leukemia virus (HTLV 1) b. feline leukemia virus. c. Rous sarcoma virus HEMATOLOGY#25 -- LEUKEMIAS OF MYELOID CELLS C. Chromosomal aberrations 1. CML: Philadelphia chromosome= translocation between #9&22 a. Oncogene c-abl (Tyr kinase) b. c-abl translocated to chrm 22 in bcr cluster c. 5' portion of bcr is fused to 3' portion of c-abl d. causes 8In TyrK activity e. bcr transcribes a ras GTPase f. bcr abl is lost in blast crises but disease continues due to other gentic abnormalities in myc, p53 HEMATOLOGY#25 -- LEUKEMIAS OF MYELOID CELLS 2. AML: DNA exchanged from long arms of chr 21 and 8;deletns on Chrm 5 or 7 3. promyelocvtic leukemia : translocation between chromosomes 17 & 15 4. acute monocytic leukemia: translocation between 9 and 11 5. oncogenesis a. normal gene which functions in cell growth and differentiation b. in normal locations in genome they are regulated by adjacent regions c. chromosomal aberration or action of RNA tumor viruses alter oncogene or its context resulting in loss of feedback control e. host factors i. hereditary ii. congenital chromosomal abnormalities iii. immune deficiency pathophysiology D. Pathophysisology 1. Failure of cells to undergo maturation and function as mature cells a. lack functional enzymes b. altered surface markers 2. cells multiply rapidly; tumor burden rapidly increases +ram just detectable to lethal in only 40 days. a. replaces functional marrow b. i. anemia ii. thrombocytopenia ==>hemorrhage iii. leukopenia ==>infection b. chronic forms take longer 3. splenomegaly, hepatomegaly, bone pain 4. meningeal leukemia
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