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Pathophysiological Scenario of Hematopoietic Disorders: A Comparative Study of Aplastic Anemia, Myelodysplastic Syndrome and Leukemia in Experimental Animals

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Abstract

The conversion of physiology to pathophysiology in hematological disorders viz: aplastic anemia, myelodysplastic syndrome (MDS) and leukemia in murine models was the subject of study in the present programme. Peripheral blood hemogram, spleno-somatic index, bone marrow smear study, cytochemical staining of marrow, cell release kinetics study during marrow explants culture, hematopoietic niche assessment, chromosomal aberration study, plasma membrane stability study of marrow cells, lysosomal membrane and mitochondrial membrane stability study and innate immune parameters were performed in the aplastic anemia, leukemia and MDS mouse model. In bone marrow aplasia, peripheral blood pancytopenia, marrow hypocellularity, decreased marrow cellular viability, deterioration of bone marrow hematopoiesis as well as hematopoietic microenvironment and extramedullary hematopoiesis were noticed. In addition, disruption of mitochondrial and lysosomal membrane integrity along with reduction of innate immune parameters were found in the hematopoietic suppressed condition. Surprisingly, no noticeable chromosomal aberration was found in the aplastic condition. Ineffective marrow hematopoiesis together with the disruption of hematopoietic microenvironment was observed in MDS. Also, extramedullary hematopoiesis, increased marrow cellular death, chromosomal aberration and loss of innate immunity were the common events. During leukemia, the number of functionally and structurally immature cells in the peripheral blood and bone marrow was increased together with malignant conversion of hematopoietic cells in the presence of malignancy supportive stromal microenvironment. Chromosomal aberration, decrease of cell mediated immunity with least mitochondrial apoptotic damage were also found in leukemic condition as well.

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Acknowledgments

Authors are thankful to the Director of Calcutta School of Tropical Medicine for her support in executing the work and also to the Department of Biotechnology, Government of West Bengal for their financial assistance {Sanction No.124 (A)-BT (Estt)/RD-3/12 dt.27.2.13}.

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    Authors and Affiliations

    1. Stem Cell Research and Application Unit, Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, C R Avenue, Kolkata, 700073, India

      Ritam Chatterjee, Sukalpa Chattopadhyay, Shalini Sanyal & Suchismita Daw

    2. Department of Biochemistry and Medical Biotechnology, Calcutta School of Tropical Medicine, Kolkata, 700073, India

      Sujata Law

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    1. Ritam Chatterjee
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    2. Sukalpa Chattopadhyay
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    3. Shalini Sanyal
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    Correspondence to Sujata Law.

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    Ritam Chatterjee and Sukalpa Chattopadhyay have contributed equally to this work.

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    Chatterjee, R., Chattopadhyay, S., Sanyal, S. et al. Pathophysiological Scenario of Hematopoietic Disorders: A Comparative Study of Aplastic Anemia, Myelodysplastic Syndrome and Leukemia in Experimental Animals. Proc Zool Soc 69, 114–124 (2016). https://doi.org/10.1007/s12595-014-0132-5

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