Differentiation and hematopoietic-support of clonal cells in myelodysplastic syndromes

Abstract

Studies were performed to obtain evidence of the differentiating and hematopoietic potential of marrow clone-original cells in patients with myelodysplastic syndromes (MDS). First, results of correlation analysis between bone marrow clonal cells and blast percentages for a total of 60 MDS showed that almost all cases had higher clonal (mean 50.1%) than blast proportion (mean 7.0%) (p < 0.001). In contrast, in 16 AML patients, mean clone/blasts disparity was nearly zero. Secondly, the amount of clone-original individual cells were defined in mature hematopoietic cells, mean 47.9% in segmented granulocytes, 47.1% in orthochromatic normoblasts and 37.8% in mature megakaryocytes. In addition, FISH examination showed approximately similar proportions of clonal cells in peripheral blood and marrow for all 22 tested cases (mean 39.1% in blood vs 49.8% in marrow). Moreover, the neutrophils in MDS peripheral blood oxidized dihydrorhodamine123 (DHR) nearly the same as neutrophils in a normal donor's circulation, while obviously poor function was observed in neutrophils from AML blood. Of note, research on clonality had an unexpected outcome as most of the typical morphological dysplastic cells possessed normal karyotypes. These findings lead to the proposal that the biological features of MDS clones are distinctive from those of AML clones.

Recurrent Abnormal Clones in Myelodysplastic Syndrome Marrow Originate from Cells at a Pluripotent Stem Level and Maintain Their Early Differentiation Potency

“…This phenomenon suggested that the majority of the clonal stem cells in MDS patients had somewhat retained their early differentiation potency but experienced difficulties in differentiating to more mature hematopoietic cells. Our results further verified our previous findings and those of other scholars regarding the blocked late differentiation of MDS clonal cells (16)(17)(18)(19). A few cases (7/46) showed that as the cells differentiated from stem cells to progenitor cells and then to advanced-stage hematopoietic cells, the clonal cell proportion increased.…”

A Combined Approach with Rituximab Plus Anti-TRAIL-R Agonistic Antibodies for the Treatment of Haematological Malignancies

“…Among the nine MoAbs and immunoconjugates approved by FDA for therapeutic indications in oncological diseases, four have been approved for the treatment of haematological malignancies. Besides rituximab, which is currently tested for B-CLL patients, alemtuzumab, a recombinant DNA-derived humanized MoAb directed against the CD52 B-cell antigen, is approved for B-CLL patients not responding to fludarabine therapy; gemtuzumab ozogamicin, a MoAb conjugated with a cytotoxic antitumour antibiotic, is indicated for CD33 + relapsed AML in patients aged over 60; dozens more are in various stages of development [119][120][121].…”

A new method for maturity-dependent fractionation of neutrophil progenitors applicable for the study of myelodysplastic syndromes

“…Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem cells characterized by cytopenia with dysplastic phenotypes of myeloid cells [1], which have been thought to result from defective differentiation [2]. However, the molecular basis of impaired differentiation is largely unclear.…”