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Abnormal morphological and functional nature of bone marrow stromal cells provides preferential support for survival of acute myeloid leukemia cells
Author(s) -
YehudaiResheff Shlomit,
AttiasTurgeman Shira,
Sabbah Rawan,
Gabay Tal,
Musallam Raneem,
FridmanDror Anna,
Zuckerman Tsila
Publication year - 2018
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32063
Subject(s) - mesenchymal stem cell , myeloid leukemia , stromal cell , bone marrow , haematopoiesis , progenitor cell , leukemia , cancer research , myeloid , cytokine , cd34 , biology , in vivo , immunology , ex vivo , stem cell , medicine , pathology , microbiology and biotechnology
Hematopoietic progenitors, residing in the bone marrow (BM) niche, are supported by mesenchymal stromal cells (MSCs). Cytogenetic and molecular aberrations in these progenitors lead to acute myeloid leukemia (AML). The BM‐MSC role in leukemogenesis is not fully elucidated. In the current study, an ex‐vivo system of patient's own stroma (POS), best mimicking the in‐vivo BM niche, has been developed aiming to unravel interactions and crosstalk between MSCs and AML cells. POS derived from AML patients at diagnosis (Dx), relapse (Rx) and remission (Rm) was compared to healthy donor MSCs in terms of their morphology, growth pattern, support of leukemia cell viability and cytokine profile. Compared to control MSCs, POS (Dx/Rx, Rm) demonstrated a reduced proliferation rate (35%), significantly slower expansion, enlarged cell area (3–4‐fold) and provided preferential support to leukemic cells of the same individual. Cytokine profiling showed significantly higher secreted phosphoprotein‐1 (SPP1) expression in Dx/Rx and Rm POS compared to healthy MSCs. Additionally, the angiopoietin‐1 expression was elevated in Dx/Rx POS with a further increase in the AML cell presence. In conclusion, the fact that POS derived in active disease and remission exhibited similar morphological and functional characteristics, might imply the involvement of the BM niche in leukemogenesis.