Chronic myeloid leukemia

Chronic myeloid leukaemia (CML) is a type of myeloproliferative neoplasm, AKA chronic myelogenous leukemia. It is driven by the bcr-abl fusion protein, detectable cytogenetically as the Philadelphia chromosome. It is a leukemia in that the fusion protein drives granulopoiesis (and less commonly megakaryopoiesis), resulting in marked peripheral blood leucocytosis.

General

• Adults - usu. 50s or 60s.

Clinical - commonly:

• Leukocytosis - neutrophils, myelocytes, metamyelocytes, +/-eosinophilia, +/-basophilia.

Progression:

1. Chronic phase - potentially curable.
2. Accelerated phase.
3. Blast crisis.

Treatment:

• Imatinib and other tyrosine kinase inhibitors

Notes:

• Myeloblast (common granulocyte precursor) -> promyelocyte -> metamyelocyte -> myelocyte -> band -> mature myelocyte.

Microscopic

Features:

• Bone marrow with too many granulocytes/granulocyte precursors.
  • Granulocyte precursors:
    1. Myeloblast (common granulocyte precursor) ~ 90% nucleus, multiple nucleoli.
       • Should be less than 10%.
    2. Promyelocyte (committed to a specific linage (neutrophil, basophil or eosinophil)) - dia. 2x mature, 40-50% nucleus, one nucleolus.
    3. Metamyelocyte - dia. 2x mature, 30-40% nucleus, no nucleolus.
    4. Myelocyte - dia. 1x mature, 50-60% nucleus - kidney bean shape, no nucleolus.
    5. Band - dia. 1x mature, 30-40% nucleus - C shape/irregular, no nucleolus.

IHC

Rarely required. CML may transform into a blast phase, typically myeloid blasts, but lymphoblasts may also be seen. These blasts are typically CD34 and/or CD117 positive. The myeloid blasts will express myeloid markers and the lymphoblasts will shows lymphoid markers.

Molecular

• t(9;22) BCR-ABL - required for diagnosis.
  • May be found in other leukemias.

See also

• Leukemia.