Increased circulating normal and BCR-ABL+Ve progenitor numbers in Philadelphia chromosome-positive acute myeloid leukaemia

Baines, Paul, Austin, Steve, Fisher, Janet, Owen-Jones, Catrin Eleri ORCID: https://orcid.org/0000-0003-0850-4724, Lee-Jones, Lisa, Throp, Duncan, Mckinley, Mark, Hoy, Terry, Mills, Ken, Thompson, Peter W. and Burnett, Alan Kenneth 2002. Increased circulating normal and BCR-ABL+Ve progenitor numbers in Philadelphia chromosome-positive acute myeloid leukaemia. Leukemia Research 26 (11) , pp. 997-1005. 10.1016/S0145-2126(02)00049-8

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Abstract

We recorded elevated numbers of circulating myeloid and erythroid colony-forming cells in 15 adult patients with acute myeloid leukaemia (AML) who presented with high blood white cell counts. Since leukaemic blasts from three of these patients were Philadelphia chromosome-positive (Ph+), we were able to determine if blood progenitors from these particular patients arose from the leukaemic clone or from residual normal progenitors. Blasts and colonies were intensively investigated using a combination of cell surface marker analysis by flow cytometry, RT-PCR and interphase fluorescence in situ hybridization (FISH). FISH detected rearrangements within the major breakpoint BCR (M-BCR) region in blasts and in some myeloid and erythroid colonies from patients 1 and 2. The minor breakpoint (m-BCR) region was detected in blasts and in some myeloid and erythroid colonies from patient 3. RT-PCR detected long b2a2 BCR-ABL transcripts in blasts from patients 1 and 2, although misspliced short e1a2 transcripts were also seen in patient 1. Only e1a2 transcripts were found in blasts from patient 3. Flow sorting demonstrated the B-cell marker CD19 on blasts and on a proportion of myeloid and erythroid progenitors from patients 1 and 3. RT-PCR also detected IgH rearrangements, further evidence of B-cell differentiation, in blasts from these two patients. We conclude that both normal and clonal circulating progenitor numbers can be raised in both M-BCR and m-BCR Ph+ AML. The underlying cause, perhaps efflux from a congested marrow, may be common to AML patients with a high blood white cell count.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Uncontrolled Keywords:	BCR-ABL, AML, Colony-forming progenitors, FISH, RT-PCR
Publisher:	Elsevier
ISSN:	0145-2126
Last Modified:	25 Oct 2022 09:31
URI:	https://orca.cardiff.ac.uk/id/eprint/58947

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