CML Flashcards
What is CML and how does it arise?
o An overproduction of myeloid precursors and mature effector cells.
o 95% of cases are due to the Philadelphia chromosome – the translocation between chromosome 9 and 22 (q34:q11) forming the fusion protein BCR-ABL1. This transcribes a constitutive tyrosine kinase involved in cell division, inhibiting DNA repair and impairing apoptosis.
What are the symptoms and their explanations?
o Typically asymptomatic in the chronic phase.
o Weight loss – this is due to the raised metabolism
o Splenomegaly – this is due to increased immature myeloid cells, particularly neutrophils being trapped in the reticuloendothelial system and in the spleen, causing enlargement.
o Pallor/anaemia – this is due to the over-proliferation of lymphoid inhibiting erythropoiesis.
What are the laboratory findings?
o Normochromic, normocytic anaemia – low RBC count and Hb.
o Hyperleukocytosis – increased number of WBCs.
o Platelet count can be normal, low or high, depending on the patient.
o Neutrophilia – increased number of neutrophils.
o High number of monocytes.
o Basophilia – increased number of basophils.
o Eosinophilia – increased number of eosinophils.
o Normal number of lymphocytes.
o Blood film shows a variety of myeloid precursors – blast cells, band cells, dysplastic cells, metamyelocytes.
What further tests can be done?
o Bone marrow aspirate – hypercellular with a high infiltration of blasts, myelocytes, band cells.
o Cytogenetics – karyotyping of chromosomes assessing genetic abnormalities, particularly the Philadelphia chromosome.
o Molecular studies – FISH and PCR to further identify the BCR-ABL1 fusion gene.
How is CML treated?
o TKIs such as imatinib – the effectiveness of this is measured by bone marrow karyotyping and blood and bone marrow molecular studies. Some patients show resistance.
o Allogenic stem cell transplant – this can be curative and has a 75% success rate.
