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Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells.

ABSTRACT: The treatment of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder has improved recently, but most patients have not yet been cured. Some patients develop resistance to the available tyrosine kinase treatments. Persistence of residual quiescent CML stem cells (LSCs) that later resume proliferation is another common cause of recurrence or relapse of CML. Eradication of quiescent LSCs is a promising approach to prevent recurrence of CML. Here we report on new biophysical differences between quiescent and proliferating CD34+ LSCs, and speculate how this information could be of use to eradicate quiescent LSCs. Using AFM measurements on cells collected from four untreated CML patients, substantial differences are observed between quiescent and proliferating cells in the elastic modulus, pericellular brush length and its grafting density at the single cell level. The higher pericellular brush densities of quiescent LSCs are common for all samples. The significance of these observations is discussed.

SUBMITTER: Guz NV

PROVIDER: S-EPMC5116407 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells.

Guz Nataliia V NV Patel Sapan J SJ Dokukin Maxim E ME Clarkson Bayard B Sokolov Igor I

Nanomedicine : nanotechnology, biology, and medicine 20160716 8

The treatment of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder has improved recently, but most patients have not yet been cured. Some patients develop resistance to the available tyrosine kinase treatments. Persistence of residual quiescent CML stem cells (LSCs) that later resume proliferation is another common cause of recurrence or relapse of CML. Eradication of quiescent LSCs is a promising approach to prevent recurrence of CML. Here we report on new biophysical differe ...[more]

PMID: 27431055

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Project description:In comparing gene expression of normal and CML CD34+ quiescent (G0) and proliferating (G1/S/G2/M) cells, 292 genes were down-regulated and 192 genes were up-regulated in the CML G0 cells. The differentially expressed genes were grouped according to their reported functions and correlations were sought with biological differences previously observed between the same groups. The most apparent correlations include: i) Normal and CML G0 cells are more primitive than G1/S/G2/M cells; ii) CML G0 cells are in a more advanced stage of development and more poised to begin proliferating than normal G0 cells; iii) When CML G0 cells are stimulated to proliferate, they undergo further differentiation and maturation more rapidly than normal G0 cells, but both granulopoiesis and erythropoiesis are less efficient than normal; iv) Whereas normal G0 cells form only granulocyte/monocyte (GM) colonies when stimulated by cytokines, CML G0 cells consistently form a combination of GM and erythroid clusters and colonies; and v) Prominin-1 (CD133) is the gene most down-regulated in CML G0 cells and its down-regulation appears to be associated with the spontaneous formation of erythroid colonies by CML progenitors without EPO. The gene most over-expressed in CML G0 cells is LepR, but its role in contributing to the myeloid expansion and other abnormalities is unknown. It was hoped that LepR might serve as a therapeutic target, but leptin had no stimulatory or inhibitory effect on either normal or CML G0 cells, our attempts to make a specific LepR antibody were unsuccessful, and no other potentially targetable over-expressed surface antigens were identified. A total of eight patients diagnosed with Ph+ CML (three in accelerated phase and five in chronic phase) were used in this study. The CML samples were all obtained from patients hospitalized at the Memorial Sloan Kettering during the period 1990-2006. The four normal bone marrow samples were purchased from Cambrex (Cambrex Bio Science Rockland,Inc., Rockland, Maine 04841, USA).

Dataset Information

Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells.

Publications

Biophysical differences between chronic myelogenous leukemic quiescent and proliferating stem/progenitor cells.

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