Autonomous proliferation and bcl-2 expression involving haematopoietic cells in patients with myelodysplastic syndrome

Abstract

Summary In this work, we investigated the autonomous proliferation, bcl-2 expression and number of apoptotic cells in the bone marrow of patients with confirmed diagnosis of myelodysplastic syndromes (MDS). Normal bone marrow cells obtained from donors of the Clinical Hospital of this university were used as a control. The autonomous proliferation, evaluated by lonal culture without exogenous growth factor, and the number of apoptotic cells in bone marrow kept for 10 days in liquid cultures at 3TC and 5% carbon dioxide, were significantly greater in MDS patients than in control subjects (P = 0.001, Wilcoxon). However, bcl-2 expression, measured by immunocytochemistry, was significantly lower in MDS patients than in normal individuals (P = 0.002, Wilcoxon). These results suggest that the high proliferation activity in MDS patients may be counteracted by the high level of medullar cell death, which might be related to the lower bcl-2 expression.

Are myelodysplastic syndromes ready for venetoclax? Exploring future potential and considerations

“…The paradox of most patients presenting with peripheral blood cytopenias despite a hypercellular bone marrow has been attributed to excessive intramedullary apoptosis of HSPC in lower risk (LR)-MDS. Several studies have demonstrated reduced BCL-2 expression and increased levels of apoptosis in HSPC from patients with early MDS subtypes compared to more advanced disease stages or healthy controls, supporting a potential role of the BCL-2-related proteins in the pathogenesis of deregulated apoptosis [12][13][14]. In particular, apoptosis exceeds proliferation with an apoptosis: proliferation ratio of 2.08 [1.15-3.63] in LR-MDS patients, whereas in disease progression this ratio is equivocal due to increasing proliferation [14].…”

Extensive myocardial infiltration by hemopoietic precursors in a patient with myelodysplastic syndrome

“…Although it may herald transformation to acute leukemia [ 25 ], this transformation may not be observed for some time [ 26 , 27 ] and sometimes not at all during follow-up [ 28 , 29 ]. Granulocyte-macrophage colony stimulating factor overproduction may lead to autonomous colony formation in the bone marrow of patients with myelodysplastic syndrome [ 30 ]; this may partially explain proliferation of malignant hemopoietic cells in the heart infiltrated by malignant cells.…”

Enhanced growth of myelodysplastic colonies in hypoxic conditions

“…Although a number of hypotheses based upon the preleukemia paradigm have been explored [24][25][26][27] The absence of a coherent mechanistic explanation for these disorders has prompted us to reexamine the assumptions behind current models of MDS [21][22][23]. The marrow of MDS patients consistently demonstrates decreased hematopoietic progenitor colonies [29][30][31][32][33][34] as well as enhanced levels of apoptosis [35][36][37][38][39][40][41][42][43][44][45][46][47]. These two findings are felt to explain the paradox of a hypercellular bone marrow with profound peripheral cytopenias observed in MDS patients [48] and suggests that a propensity to apoptosis is responsible for the initiation of these disorders.…”