PMID- 12363468 OWN - NLM STAT- MEDLINE DCOM- 20021209 LR - 20190826 IS - 0145-2126 (Print) IS - 0145-2126 (Linking) VI - 26 IP - 11 DP - 2002 Nov TI - Increased circulating normal and BCR-ABL+Ve progenitor numbers in Philadelphia chromosome-positive acute myeloid leukaemia. PG - 997-1005 AB - 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. FAU - Baines, Paul AU - Baines P AD - Haematology Department, University Hospital of Wales, CF14 4XW, Cardiff, UK. bainesp@cf.ac.uk FAU - Austin, Steve AU - Austin S FAU - Fisher, Janet AU - Fisher J FAU - Owen-Jones, Eleri AU - Owen-Jones E FAU - Lee-Jones, Lisa AU - Lee-Jones L FAU - Throp, Duncan AU - Throp D FAU - Mckinley, Mark AU - Mckinley M FAU - Hoy, Terry AU - Hoy T FAU - Mills, Ken AU - Mills K FAU - Thompson, Peter AU - Thompson P FAU - Burnett, Alan AU - Burnett A LA - eng PT - Comparative Study PT - Journal Article PL - England TA - Leuk Res JT - Leukemia research JID - 7706787 RN - 0 (Biomarkers, Tumor) RN - 0 (DNA, Neoplasm) RN - 0 (Oncogene Proteins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (RNA, Messenger) RN - 0 (RNA, Neoplasm) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.2 (Fusion Proteins, bcr-abl) RN - EC 2.7.11.1 (BCR protein, human) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-bcr) SB - IM CIN - Leuk Res. 2002 Nov;26(11):971-3. PMID: 12363461 MH - Acute Disease MH - Adult MH - Biomarkers, Tumor MH - Case-Control Studies MH - Colony-Forming Units Assay MH - DNA, Neoplasm/analysis MH - Erythroid Precursor Cells/*metabolism MH - Flow Cytometry MH - Fusion Proteins, bcr-abl/blood/*genetics MH - Genes, Immunoglobulin/genetics MH - Humans MH - In Situ Hybridization, Fluorescence MH - Karyotyping MH - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*genetics/metabolism MH - Leukocyte Count MH - Myeloid Progenitor Cells/*metabolism MH - Oncogene Proteins/genetics/metabolism MH - *Protein-Tyrosine Kinases MH - *Proto-Oncogene Proteins MH - Proto-Oncogene Proteins c-bcr MH - RNA, Messenger/genetics MH - RNA, Neoplasm/genetics/metabolism MH - Reverse Transcriptase Polymerase Chain Reaction EDAT- 2002/10/05 04:00 MHDA- 2002/12/10 04:00 CRDT- 2002/10/05 04:00 PHST- 2002/10/05 04:00 [pubmed] PHST- 2002/12/10 04:00 [medline] PHST- 2002/10/05 04:00 [entrez] AID - S0145212602000498 [pii] AID - 10.1016/s0145-2126(02)00049-8 [doi] PST - ppublish SO - Leuk Res. 2002 Nov;26(11):997-1005. doi: 10.1016/s0145-2126(02)00049-8.