Polyclonal normal hematopoietic progenitors in patients with acute myeloid leukemia.
OBJECTIVE
To study the clonality of cytogenetically normal progenitors detected in the peripheral blood (PB) of acute myeloid leukemia (AML) patients.


METHODS
Five female patients with cytogenetically abnormal, newly-diagnosed AML who were heterozygous for informative alleles of the androgen receptor (AR) gene were studied using the human androgen receptor allele (HUMARA) assay.


RESULTS
PB mononuclear cells and bone marrow (BM) fibroblasts from these patients were monoclonal and polyclonal, respectively. Both cytogenetically normal and abnormal colony-forming cells (CFC) were detected from 3 AML samples and the HUMARA assay determined that most of these CFC were part of the leukemic clone. The fourth sample generated colonies that were 100% normal by cytogenetics and polyclonal by HUMARA. In contrast, 5-week-old long-term culture (LTC)-derived colonies were 100% cytogenetically normal by FISH and polyclonal by HUMARA in 4 of the 5 samples. The fifth sample, which showed a small number of karyotypically abnormal LTC-derived colonies, nevertheless showed amplification of the "leukemia-associated" AR allele in 46/50 LTC-derived colonies as well as all 40 directly clonogenic cells tested.


CONCLUSIONS
Thus in 4 of 5 AML samples tested, both cytogenetics and the HUMARA assay indicate that a substantial number of normal, polyclonal hematopoietic progenitors often persist in AML PB at diagnosis in spite of the predominance of malignant blasts and the severe cytopenias of normal mature blood cells that are typically seen clinically.
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
Yinghui
Y
Guan
Steven
S
Ralph
Donna E
DE
Hogge
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000483:Alleles; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000737:chemistry / Q000473:pathology; D002478:Cells, Cultured / Q000737:chemistry / Q000473:pathology; D002869:Chromosome Aberrations; D002999:Clone Cells / Q000737:chemistry / Q000473:pathology; D004303:Dosage Compensation, Genetic; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000473:pathology; D005784:Gene Amplification; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000473:pathology*; D006579:Heterozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology; D011944:Receptors, Androgen / Q000032:analysis
D015415:Biomarkers; D011944:Receptors, Androgen