Abstract
Background and Objectives Chronic myeloid leukemia (CML) is characterized by hyperproliferation of myeloid precursors, increased fibrosis, and neoangiogenesis in the bone marrow. Imatinib inhibits BCR-ABL tyrosine kinase produced due to reciprocal translocation t(9;22) in neoplastic CML cells. It reduces hyperproliferation of myeloid precursors and has been found to affect bone marrow fibrosis and angiogenesis. This study was done to assess the effect of imatinib on bone marrow morphology and angiogenesis in CML. Methods 31 newly diagnosed CML patients were evaluated before and after 3 months of imatinib therapy. A marrow morphological response (MMR) score was used to assess marrow cytological and histological features including grade of fibrosis. Mean microvessel density (MVD) was also assessed. Hematological parameters and BCR-ABL transcript levels were assessed in the peripheral blood. Results 86.21% of patients showed decrease in marrow cellularity with normalization of M:E ratio. 72.42% of patients had decrease in grade of fibrosis and 17.24% showed no change while 10.34% of patients showed progression of fibrosis grade. Patients with MMR score ≥ 2 (n=4) and those with progression of fibrosis grade (n=3) showed suboptimal molecular response (BCR-ABL transcripts > 10%). Pretherapy mean MVD of patients (14.69 ± 5.28) was higher than that of controls (6.32 ± 1.64). A significant reduction of 66.51% was observed in posttherapy mean MVD (4.98 ± 2.77) of CML patients (p<0.001). Conclusion Imatinib therapy in CML not only decreases marrow cellularity, but also helps towards normalization of bone marrow microenvironment by reducing fibrosis and angiogenesis.
Highlights
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by excessive accumulation of apparently normal myeloid cells in the bone marrow and peripheral blood
It is associated with the presence of Philadelphia chromosome, which is the result of a reciprocal translocation between chromosomes 9 and 22 resulting in the formation of BCR-ABL chimeric protein which has uncontrolled tyrosine kinase activity [1]
Imatinib mesylate is a selective BCR-ABL protein tyrosine kinase inhibitor which acts by binding to the ATP binding site of BCR-ABL tyrosine kinase, causing its inactivation and thereby effecting apoptosis of leukemic cells which leads to improvement in bone marrow hematological and morphological parameters [3, 4]
Summary
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by excessive accumulation of apparently normal myeloid cells in the bone marrow and peripheral blood. It is associated with the presence of Philadelphia chromosome, which is the result of a reciprocal translocation between chromosomes 9 and 22 resulting in the formation of BCR-ABL chimeric protein which has uncontrolled tyrosine kinase activity [1]. Points 0 1 0 1 0 1 0 1 0 1 0 0 1 0 0 to assess morphological changes and changes in angiogenesis in the bone marrow in patients of CML on imatinib mesylate therapy
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