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Chronic Myelogenous Leukemia

Chronic Myelogenous Leukemia. Definition. Myeloid Leukemias are heterogenous group of diseases characterized by infiltration of the blood, bone marrow, and other tissues by neoplastic cells of the hemopoietic system. Source: p. 683. Chronic Myelogenous Leukemia.

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Chronic Myelogenous Leukemia

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  1. Chronic Myelogenous Leukemia

  2. Definition • Myeloid Leukemias are heterogenous group of diseases characterized by infiltration of the blood, bone marrow, and other tissues by neoplastic cells of the hemopoietic system. Source: p. 683

  3. Chronic Myelogenous Leukemia • Clonal expansion possessing reciprocal translocation between chromosomes 9 and 22 • Results into head-tail fusion of BCR gene on chr 22q11 with ABL located on 9q34.

  4. Incidence • 1.5 per 100,000 people per year. • Higher incidence in men than in women • Increases slowly with age until the mid 40’s  where it rises rapidly Source: p. 683

  5. Etiology • Cigarette smoking accelerated the progression to blast crisis  adversely affected survival • No clear correlation with exposure to cytotoxicdrugs, or viral infection. • Only large doses of radiation can induce CML. Source: p. 683

  6. Pathophysiology translocation between the long arms of chromosomes 22 and 9; t(9;22) Relocation of ABLoncogene from the long arm of chromosome 9 to the long arm of chromosome 22 in the BCR region BCR/ABL fusion gene encodes a chimeric protein with strong tyrosine kinase activity. chronic myelogenous leukemia (CML) phenotype http://emedicine.medscape.com/article/199425-overview

  7. Disease Progression • t(9:22) • Trisomy 8 • 17p-(p53 loss) *acquisition of these genetic and/or molecular abnormalities is critical to the phenotypic transformation. Source: p. 683

  8. Source: p. 683 • Disease progression • Heterogenous structural alterations of p53 gene • Structural alterations and lack of protein production of the retinoblastoma gene • Catalytic component of telomerase • Shorter survival times • Associated with large deletions adjacent to the translocation breakpoint on the derivative 9 chromosome.

  9. Blastic transformation • Progressive de novo DNA methylation at the BCR/ABL locus • Hypomethylation of the LINE-1 retrotransposon promoter • Functional inactivation of the tumor suppressor protein phospholipaseA2 • Interleukin 1B Source: p. 683 - 684

  10. Clinical Features Source: p. 684

  11. Presenting symptoms • Gum bleeding • Pallor • Easy fatigability • Malaise

  12. ROS • Weightloss without anorexia • Early satiety and abdominal fullness • Occasional feelings of feverishness • Medical History • LMP: 4 days, profuse flow, longer and stronger than the usual • Physical Exam • PR 112 bpm • Pale palpebral conjunctivae • Palpable spleen 4cm from the left subcostal along MCL • Petechiae over both lower extremities

  13. Laboratory exams • CBC: Hb 72g/dl, Hct 0.20, WBC162x109/L,

  14. Physical Findings Source: p. 684

  15. Hematologic Findings Source: p. 684

  16. Chromosomal Findings Source: p. 684

  17. Progression of CML

  18. Complications of CML Disease Acceleration Blast Crisis (Acute Leukemia) • Unexplained fever • Significant weight loss • Increasing dose requirement of the drugs controlling the disease • Bone and joint pain • Bleeding • Thrombosis • Infections Source: p. 684

  19. Treatment

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