Clinical Haematology Service

Kolkata, India

Clinical Haematology Service

Kolkata, India

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Chowdhury S.,Council of Scientific and Industrial Research Indian Institute of Chemical Biology | Mandal C.,Council of Scientific and Industrial Research Indian Institute of Chemical Biology | Sarkar S.,Council of Scientific and Industrial Research Indian Institute of Chemical Biology | Bag A.K.,Council of Scientific and Industrial Research Indian Institute of Chemical Biology | And 2 more authors.
Leukemia Research | Year: 2012

Childhood acute lymphoblastic leukaemia is characterized by aberrant proliferation and accumulation of malignant lymphoblasts in bone marrow (BM), followed by their migration into circulation. An enhanced cell-surface expression of ALL-associated 9-O-acetylated sialoglycoproteins (Neu5,9Ac 2-GPs) was demonstrated. Present investigation reports a positive correlation between the increased density of Neu5,9Ac 2-GPs on lymphoblasts and their mobilization from BM involving enhanced Neu5,9Ac 2 on CD45 demonstrating modulation of FAK and ERK molecules. In contrast, a small population of cells, identified as haematopoietic precursors, with comparatively lesser Neu5,9Ac 2-GPs showed increased binding towards BM stroma. Thus, Neu5,9Ac 2-GPs is a developmentally regulated oncofoetal antigen, whose up-regulation is imperative in the interaction between lymphoblasts and BM stroma, governing their mobilization into circulation. © 2011 Elsevier Ltd.


Chowdhury S.,Council of Scientific and Industrial Research Indian Institute of Chemical Biology | Chandra S.,Clinical Haematology Service | Mandal C.,Council of Scientific and Industrial Research Indian Institute of Chemical Biology
Glycoconjugate Journal | Year: 2014

Childhood acute lymphoblastic leukaemia (ALL) originates from mutations in haematopoietic progenitor cells (HPCs). For high-risk patients, treated with intensified postremission chemotherapy, haematopoietic stem cell (HSC) transplantation is considered. Autologous HSC transplantation needs improvisation till date. Previous studies established enhanced disease-associated expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) on lymphoblasts of these patients at diagnosis, followed by its decrease with clinical remission and reappearance with relapse. Based on this differential expression of Neu5,9Ac2-GPs, identification of a normal HPC population was targeted from patients at diagnosis. This study identifies two distinct haematopoietic progenitor populations from bone marrow of diagnostic ALL patients, exploring the differential expression of Neu5,9Ac2-GPs with stem cell (CD34, CD90, CD117, CD133), haematopoietic (CD45), lineage-commitment (CD38) antigens and cytosolic aldehyde dehydrogenase (ALDH). Normal haematopoietic progenitor cells (ALDH+SSCloCD45hiNeu5,9Ac2- GPsloCD34+CD38-CD90+CD117+CD133+) differentiated into morphologically different, lineage-specific colonies, being crucial for autologous HSC transplantation while leukemic stem cells ( ALDH+SSCloCD45loNeu5,9 Ac2 - GPshiCD34+CD38+CD90-CD117-CD133-) lacking this ability can be potential targets for minimal residual disease detection and drug-targeted immunotherapy. © Springer Science+Business Media New York 2014.

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