Chronic myelogenous leukemia pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Badria Munir M.B.B.S.[2] Mohamad Alkateb, MBBCh [3] Sima NoorAli, M.D.


Chronic myeloid leukemia (CML), a myeloproliferative disorder, which is characterized by the uncontrolled expansion of immature bone marrow cells of myeloid origin.The hallmark of CML is the formation of the Philadelphia chromosome resulting from the reciprocal translation (9;22)(q34;q11.2), resulting in a derivative 9q+ and a small 22q- ultimately forms a BCR/ABL fusion gene and production of a BCR/ABL fusion protein. The gene product of the BCR/ABL gene constitutively activates numerous downstream targets including c-myc, Akt and Jun, all of which cause uncontrolled proliferation and survival of CML cells.


Genetic Translocation:

Role of reactive oxygen species:

Altered bone marrow pathway signalling:

Role of Integrin:

Blast crisis:

  • Chronic myeloid leukemia (CML) in blast crisis is the transition of CML in chronic or accelerated phase to an acute leukemia.
  • It is characterized by:
  • In light of recent changes in the World Health Organization, definition of acute leukemia, the percentage of blasts required for CML in blastic phase may someday be reduced to 20%.[16]
  • Consistent with the early stem cell nature of CML, blastic transformation may be:
  • Myeloid blast crisis being about two times more common than lymphoid.
Genetic Alterations in Blast crisis:
  • Following genetic changes have been observed which play crucial role in progression of disease phase.
  • Recent studies have implicated activation of the following pathways [21]

Gross Pathology

On gross pathology, no distinctive findings are seen in chronic myeloid leukemia.

Microscopic Pathology

Blast cells are seen on peripheral blood smear of patients of chronic myeloid leukemia which are present during blast crisis.


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