Differences in the composition and in the efficiency of red cell production of normal and CML erythroid progenitor populations are highlighted by response to human c-kit ligand Journal Article

  

Authors:	Strife, A.; Perez, A.; Lambek, C.; Wisniewski, D.; Bruno, S.; Darzynkiewicz, Z.; Clarkson, B.
Article Title:	Differences in the composition and in the efficiency of red cell production of normal and CML erythroid progenitor populations are highlighted by response to human c-kit ligand
Abstract:	Previous studies have suggested that erythroid progenitors derived from patients with chronic myelogenous leukemia (CML) in chronic phase may have reduced proliferative capacity. Considering recent evidence that mast cell growth factor (MGF) enhances the proliferative capacity of normal erythroid burst-forming units (BFU-E), we examined whether MGF could increase the proliferative potential of CML erythroid progenitors to normal capacity. To evaluate the total proliferative capacity achieved, the BFU-E were divided into four subpopulations (XL = extra large, L = large, M = medium, S = small) and colonies were aspirated to determine the cellularity of BFU-E from each subpopulation. MGF alone or in combination with MoT cell line conditioned medium (MoCM) or granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-3 (IL-3) significantly increased the proliferative capacity of erythropoietin (EPO) dependent CML and normal BFU-E. Although the total number of BFU-E generated were similar, the number of BFU-E with high proliferative potential were considerably less in CML BFU-E populations. BFU-E designated XL (129,000-431,000 cells) were only found in MGF cultures and only normal BFU-E had this proliferative capacity. BFU-E designated L were increased in both normal and CML BFU-E populations but less CML BFU-E had this proliferative capacity (mean number 25% of normal) and CML L BFU-E from 2 3 CML patients comprised fewer cells than normal L BFU-E. Normal BFU-E populations comprised 16-24% high proliferative BFU-E (XL + L) in contrast to 4-5% high proliferative BFU-E (L only) comprising CML BFU-E populations. This shift resulted in 78-87% of CML erythroid cells being generated by low proliferative BFU-E in contrast to the normal state in which 63-71% of erythroid cells are generated by high proliferative BFU-E. A possible explanation for the difference in the final effect of the Ph1 translocation on the granulocyte and erythroid lineages is proposed. © 1993.
Keywords:	controlled study; human cell; chronic myelogenous leukemia (cml); cell proliferation; cells, cultured; stem cell factor; erythropoietin; cell maturation; erythroid precursor cell; erythropoiesis; granulocyte macrophage colony stimulating factor; tumor cells, cultured; cell population; chronic myeloid leukemia; cell subpopulation; chromosome translocation; cell size; philadelphia 1 chromosome; erythroid progenitor cells; colony formation; chronic leukemia; philadelphia chromosome; interleukin 3; burst forming unit e; leukemia, myeloid, chronic; c-kit ligand; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; hematopoietic cell growth factors; bfu-e
Journal Title:	Leukemia Research
Volume:	17
Issue:	9
ISSN:	0145-2126
Publisher:	Elsevier Ltd
Date Published:	1993-09-01
Start Page:	799
End Page:	807
Language:	English
DOI:	10.1016/0145-2126(93)90115-2
PUBMED:	7690436
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0027430113&doi=10.1016%2f0145-2126%2893%2990115-2&partnerID=40&md5=92a2450e886fa0403e967b0999f24c5d
Notes:	Article -- Export Date: 1 March 2019 -- Source: Scopus

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