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

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.

Quercetin induces autophagy in myelodysplastic bone marrow including hematopoietic stem/progenitor compartment

“…The paradox arises as there is hyperproliferation with significant increase in apoptosis. The paradoxical expression of specific markers of the bone marrow HSPC's can be associated with the histologic and peripheral blood hemogram results as the H&E stained bone marrow depicted typical infiltration of dysplastic blast cells (Figure 1I,II,V,VI) although there was peripheral blood neutropenia 41,42 . Previously, it was also noted that there was a sharp increase in erythroblast marker CD71 but at the same time blood is anemic lacking functional RBC 41 .…”

“…N3385) at a dose of 80 mg/kg and kept for 1½ month for proper development of the disease features. The control group of animals received equal volume of 0.9% NaCl 11,12,41‐44 …”

“…JGB is an indirect method to determine the dysfunction of mitochondria because when mitochondrial membrane will rupture the contents will come out in cytosol causing colorant oxidation. In brief, the bone marrow smears were air dried and stained in 0.1% JGB solution in normal saline at 37°C for 5‐7 minutes washed and observed under 400× magnification at light microscope (Olympus, Ch20i, Japan) 42 …”

Morphogen signaling by Wnt/β‐catenin pathway and microenvironmental alteration in the bone marrow of agricultural pesticide exposure‐induced experimental aplastic anemia

“…[42,43] was scored manually and represented as percentage of phagocytosis (primed macrophage × 100/total number of macrophage). [44] 2.5 | BM isolation, marrow smear, and single cell preparation…”

IL-3 and GM-CSF in combination alters protein tyrosine kinase activity of splenic macrophages in leukemic mice.

“…Leukemia control mice are produced by challenging in intraperitoneally injected with ENU at 80 mg/Kg body weight at -3 weeks old condition twice in one week interval [15,16].…”