The development of Gleevec: A success story

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11 Apr 2012
All blood cells arise from one kind of multipotent stem cell
e.g. multipotent hemopoietic stem cell progenitor lymphoid OR myeloid progenitor
Type of leukemia depends on defects of specific progenitors.
Normal cell pathway: terminal differentiation
Cancer cells: stem cells/daughter cells fail to differentiation. Proliferate and form tumor.
Leukemia: cancer of blood/bone marrow characterized by abnormal proliferation of blood
cells (usually WBCs, leukocytes)
Chronic Myeloid Leukemia (CML)
Myeloproliferative disorder
Median age 53
Nonspecific symptoms, hard to detect
Massive clonal proliferation of myeloid cells
Biphasic: chronic (stable) phase blast phase
3 Phases in CML
Phase 1 : Chronic ~4-6years
oExpansion of WBCs, cells still differentiate to certain degree and WBC
function is normal
oMinor symptoms (asymptomatic)
oSlow progression
Phase 2 Accelerated ~up to 1 year
oFurther mutation: increased WBC, harder to treat
Phase 3; Terminal ~ survival 3-6 months
oMyeloid blast crisis
oProgenitors unable to differentiate
Treatment of CML
Chemotherapy (Hydroxyurea)
oControl leukocytosis (raised WBC count), spenomegaly (enlargement of
speen) in chronic phase
oNo effect on progression to blast crisis
oNon-selective, not very effective
oMny side effects
omodest prolongation of survival
oBoosts immune system
oInterferons combat viruses, bacteria
Allogenic bone marrow transplantation
oOnly potentially curative
oAcute mortality
oSome risks rejection
Philadelphia Chromosome
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