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

Leuk Res. 2002 Nov;26(11):997-1005. doi: 10.1016/s0145-2126(02)00049-8.

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.

Publication types

  • Comparative Study

MeSH terms

  • Acute Disease
  • Adult
  • Biomarkers, Tumor
  • Case-Control Studies
  • Colony-Forming Units Assay
  • DNA, Neoplasm / analysis
  • Erythroid Precursor Cells / metabolism*
  • Flow Cytometry
  • Fusion Proteins, bcr-abl / blood
  • Fusion Proteins, bcr-abl / genetics*
  • Genes, Immunoglobulin / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Karyotyping
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism
  • Leukocyte Count
  • Myeloid Progenitor Cells / metabolism*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins c-bcr
  • Proto-Oncogene Proteins*
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • BCR protein, human
  • Proto-Oncogene Proteins c-bcr