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Evaluation of ‘discordant maturation’ in chronic myeloid leukaemia using cultures of primitive progenitor cells and their production of clonogenic progeny (CFU‐GM)
Author(s) -
Marley S. B.,
Lewis J. L.,
Scott M. A.,
Goldman J. M.,
Gordon M. Y.
Publication year - 1996
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.1996.d01-1910.x
Subject(s) - clonogenic assay , cfu gm , progenitor cell , myeloid leukaemia , biology , chronic myeloid leukaemia , myeloid , immunology , progenitor , cancer research , stem cell , cell culture , genetics
The ‘discordant maturation hypothesis’ proposes that the most mature proliferating cells in chronic‐phase chronic myeloid leukaemia (CML) are responsible for the expansion of the Ph‐positive population. To evaluate this hypothesis we used a delta assay for primitive haemopoietic cells (PΔ assay for PΔ cells) which allows investigation of the kinetics of granulocyte‐macrophage progenitor (CFU‐GM) production. The frequencies of these primitive (PΔ) cells were similar in CML blood (14.5/10 5 mononuclear cells), CML marrow (17.3/10 5 ) and normal marrow (11.6/10 5 ) The average frequency in normal blood is only 0.58/10 6 . The absolute numbers of PΔ cells in CML patients are therefore greatly increased. The average numbers of CFU‐GM produced by individual PΔ cells were reduced in CML blood (8.1) and marrow (11.6) compared with normal marrow (28.5). This is consistent with a reduced probability of differentiation at the single cell level in CML. Although the absolute number of CFU‐GM produced by individual CML PΔ cells was subnormal there was a relative increase in the number of day 7 CFU‐GM compared with the number of day 14 and 21 CFU‐GM, which agrees with the ‘discordant maturation hypothesis’. This bias towards day 7 colony formation could reflect accelerated maturation by the CFU‐GM produced by PΔ cells or, alternatively, the production of CFU‐GM with shorter than normal maturation pathways. Overall, these results suggest that discordant maturation does not by itself account for myeloid expansion in CML. It is more likely that myeloid expansion in CML is due mainly to an increase in the number of primitive haemopoietic progenitor cells.