Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia

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 r...

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Main Authors: Neetu Pandey, Geeta Yadav, Rashmi Kushwaha, Shailendra Prasad Verma, Uma Shankar Singh, Ashutosh Kumar, Prabhaker Mishra
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Advances in Hematology
Online Access:http://dx.doi.org/10.1155/2019/1835091
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author Neetu Pandey
Geeta Yadav
Rashmi Kushwaha
Shailendra Prasad Verma
Uma Shankar Singh
Ashutosh Kumar
Prabhaker Mishra
author_facet Neetu Pandey
Geeta Yadav
Rashmi Kushwaha
Shailendra Prasad Verma
Uma Shankar Singh
Ashutosh Kumar
Prabhaker Mishra
author_sort Neetu Pandey
collection DOAJ
description 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.
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spelling doaj-art-a3e79aba95094806a01b41c8a348644b2025-02-03T01:31:18ZengWileyAdvances in Hematology1687-91041687-91122019-01-01201910.1155/2019/18350911835091Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid LeukemiaNeetu Pandey0Geeta Yadav1Rashmi Kushwaha2Shailendra Prasad Verma3Uma Shankar Singh4Ashutosh Kumar5Prabhaker Mishra6Department of Pathology, King George’s Medical University, Lucknow, U.P. 226003, IndiaDepartment of Pathology, King George’s Medical University, Lucknow, U.P. 226003, IndiaDepartment of Pathology, King George’s Medical University, Lucknow, U.P. 226003, IndiaDepartment of Clinical Hematology, King George’s Medical University, Lucknow, U.P. 226003, IndiaDepartment of Pathology, King George’s Medical University, Lucknow, U.P. 226003, IndiaDepartment of Pathology, King George’s Medical University, Lucknow, U.P. 226003, IndiaDepartment of Biostatistics & Health Informatics, Sanjay Gandhi Post Graduate of Medical Sciences, Raebareli Road, Lucknow, U.P. 226014, IndiaBackground 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.http://dx.doi.org/10.1155/2019/1835091
spellingShingle Neetu Pandey
Geeta Yadav
Rashmi Kushwaha
Shailendra Prasad Verma
Uma Shankar Singh
Ashutosh Kumar
Prabhaker Mishra
Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia
Advances in Hematology
title Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia
title_full Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia
title_fullStr Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia
title_full_unstemmed Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia
title_short Effect of Imatinib on Bone Marrow Morphology and Angiogenesis in Chronic Myeloid Leukemia
title_sort effect of imatinib on bone marrow morphology and angiogenesis in chronic myeloid leukemia
url http://dx.doi.org/10.1155/2019/1835091
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