BCR-ABL, ABL-BCR, BCR, and ABL genes are all expressed in individual granulocyte-macrophage colony-forming unit colonies derived from blood of patients with chronic myeloid leukemia

Blood. 1995 Apr 15;85(8):2171-5.

Abstract

It has been suggested that the BCR-ABL gene of chronic myeloid leukemia (CML) is not uniformly expressed in Philadelphia (Ph)-positive cells, and that BCR-ABL gene expression precludes transcription of the normal BCR or ABL genes. Therefore, we have analyzed granulocyte-macrophage colony-forming unit (CFU-GM) colonies derived from peripheral blood of 11 CML patients by cytogenetic and by reverse transcriptase-polymerase chain reaction (PCR) amplification of BCR-ABL, ABL-BCR, BCR, and ABL. All CFU-GM colonies with analyzable metaphases were found to contain a Ph chromosome. In 2 patients, the initial PCR screening failed to detect BCR-ABL transcripts in 2 of 11 and 1 of 7 Ph-positive colonies. However, when amplification for BCR-ABL was repeated in quintuplicate, all but 1 colony from a single patient showed one or more positive results. Amplifications of the four genes in each colony showed that BCR-ABL, ABL-BCR, and the normal BCR and ABL were simultaneously expressed in the majority of CFU-GM colonies. Replicate PCR tests for BCR and for ABL in colonies initially scored as negative also uncovered previously undetected positive amplifications. We conclude that BCR-ABL expression does not suppress transcription from the normal BCR and ABL genes, and that Ph-positive, BCR-ABL-negative colonies derived from peripheral blood CFU-GM are rare or nonexistent.

MeSH terms

  • Base Sequence
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Clone Cells / metabolism*
  • Clone Cells / pathology
  • Fusion Proteins, bcr-abl / biosynthesis*
  • Fusion Proteins, bcr-abl / genetics
  • Gene Expression Regulation, Leukemic*
  • Granulocytes / metabolism*
  • Granulocytes / pathology
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology*
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / blood
  • Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / pathology
  • Leukemia, Myeloid, Chronic-Phase / blood
  • Leukemia, Myeloid, Chronic-Phase / pathology*
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Molecular Sequence Data
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • Neoplastic Stem Cells / metabolism*
  • Oncogene Proteins / biosynthesis*
  • Oncogene Proteins / genetics
  • Philadelphia Chromosome
  • Polymerase Chain Reaction
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins c-abl / biosynthesis*
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-bcr
  • Proto-Oncogene Proteins*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / analysis
  • RNA, Neoplasm / genetics
  • Tumor Stem Cell Assay

Substances

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