Ch 32: Myeloproliferative neoplasms

Myeloproliferative neoplasms

clonal hematopoietic disorders caused by genetic mutation in HSCs resulting in expansion, excessive production, and accumulation of mature erythrocytes, granulocytes and platelets

Chronic Myeloid Leukemia

• BCR::ABL1 positive neoplasm

• neutrophilia

• left-shift to include all stages of myeloid development

• presence of Philadelphia (Ph) chromosome translocation or BCR::ABL1 fusion gene

If untreated, progresses as an Acute Leukemia

• AML

• ALL

CML

arises from a single genetic translocation in pluripotential HSC producing a clonal overproduction of the myeloid cell

• Begins with chronic clinical phase

• if untreated: Clinical features: Frequent infection, Anemia, Bleeding, Splenomegaly

• Seen predominantly in ages 46 to 53 years

• Represents 15-20% of all cases of leukemia

• Slightly more common in men than in women

• Symptom associated with clinical onset:

  • fatigue

  • decreased tolerance of exertion

  • anorexia

  • abdominal discomfort

  • weight loss

  • symptomatic effects from splenic enlargement

Imatinib

it is a tyrosine kinase inhibitor (TKI) that has chaned prognosis and treatment for CML

Nowell and Hungerford

they were the first to discover Philadelphia chromosome identified as short chromosome 22 (1960)

Rowley

(1970) Philadelphia chromosome is a reciprocal translocation between the long arms of chromosome 9 and 22

BCR::ABL1

• Translocation of an ABL1 proto-oncogene from band q34 of chromosome 9 to the BCR of band q11 of chromosome 22

• Produces p210 BCR::ABL1

  • expresses enhanced tyrosine kinase activity from the ABL1 moiety

  • this gene also produces 210-kD BCR::ABL1 fussion protein (p210 BCR::ABL1)

t(9;22) translocation

produces BCR::ABL1 chimeric gene

T

T/F: BCR::ABL1 negative MPNs are related based on Janus kinase 2 mutation & Absence of Philadelphia chromosome

Essential Thrombocythemia

Polycythemia vera

Primary myelofibrosis

Chronic Neutrophilic Leukemia

Chronic Eosinophilic Leukemia

Juvenile myelomonocytic leukemia

Myeloproliferative neoplasm-not otherwise specified/MPN-NOS

Chronic phase

MPNs begin as stable, manageable and has slow progression