Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow

T. Leemhuis, D. Leibowitz, G. Cox, R. Silver, Edward Srour, G. Tricot, R. Hoffman

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Abstract

Chronic myeloid leukemia (CML) is a malignant disorder of the hematopoietic stem cell. It has been shown that normal stem cells coexist with malignant stem cells in the bone marrow of patients with chronic-phase CML. To characterize the primitive hematopoietic progenitor cells within CML marrow, CD34+DR- and CD34+DR+ cells were isolated using centrifugal elutriation, monoclonal antibody labeling, and flow cytometric cell sorting. Polymerase chain reaction analysis of RNA samples from these CD34+ subpopulations was used to detect the presence of the BCR/ ABL translocation characteristic of CML. The CD34+DR+ subpopulation contained BCR/ABL(+) cells in 11 of 12 marrow samples studied, whereas the CD34+DR- subpopulation contained BCR/ABL(+) cells in 6 of 9 CML marrow specimens. These cell populations were assayed for hematopoietic progenitor cells, and individual hematopoietic colonies were analyzed by PCR for their BCR/ABL status. Results from six patients showed that nearly half of the myeloid colonies cloned from CD34+DR- cells were BCR/ABL(+), although the CD34+DR- subpopulation contained significantly fewer BCR/ABL(+) progenitor cells than either low-density bone marrow (LDBM) or the CD34+DR+ fraction. These CD34+ cells were also used to establish stromal cell-free long-term bone marrow cultures to assess the BCR/ABL status of hematopoietic stem cells within these CML marrow populations. After 28 days in culture, three of five cultures initiated with CD34+DR- cells produced BCR/ABL(-) cells. By contrast, only one of eight cultures initiated with CD34+DR+ cells were BCR/ABL(-) after 28 days. These results indicate that the CD34+DR- subpopulation of CML marrow still contains leukemic progenitor cells, although to a lesser extent than either LDBM or CD34+DR+ cells.

Original languageEnglish (US)
Pages (from-to)801-807
Number of pages7
JournalBlood
Volume81
Issue number3
StatePublished - Feb 1 1993

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Hematopoietic Stem Cells
Stem cells
Bone
Bone Marrow
Cells
Stem Cells
Polymerase chain reaction
Sorting
Labeling
Monoclonal Antibodies
RNA
Leukemia, Myeloid, Chronic Phase
Polymerase Chain Reaction
Stromal Cells
Population

ASJC Scopus subject areas

  • Hematology

Cite this

Leemhuis, T., Leibowitz, D., Cox, G., Silver, R., Srour, E., Tricot, G., & Hoffman, R. (1993). Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow. Blood, 81(3), 801-807.

Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow. / Leemhuis, T.; Leibowitz, D.; Cox, G.; Silver, R.; Srour, Edward; Tricot, G.; Hoffman, R.

In: Blood, Vol. 81, No. 3, 01.02.1993, p. 801-807.

Research output: Contribution to journalArticle

Leemhuis, T, Leibowitz, D, Cox, G, Silver, R, Srour, E, Tricot, G & Hoffman, R 1993, 'Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow', Blood, vol. 81, no. 3, pp. 801-807.
Leemhuis T, Leibowitz D, Cox G, Silver R, Srour E, Tricot G et al. Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow. Blood. 1993 Feb 1;81(3):801-807.
Leemhuis, T. ; Leibowitz, D. ; Cox, G. ; Silver, R. ; Srour, Edward ; Tricot, G. ; Hoffman, R. / Identification of BCR/ABL-negative primitive hematopoietic progenitor cells within chronic myeloid leukemia marrow. In: Blood. 1993 ; Vol. 81, No. 3. pp. 801-807.
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abstract = "Chronic myeloid leukemia (CML) is a malignant disorder of the hematopoietic stem cell. It has been shown that normal stem cells coexist with malignant stem cells in the bone marrow of patients with chronic-phase CML. To characterize the primitive hematopoietic progenitor cells within CML marrow, CD34+DR- and CD34+DR+ cells were isolated using centrifugal elutriation, monoclonal antibody labeling, and flow cytometric cell sorting. Polymerase chain reaction analysis of RNA samples from these CD34+ subpopulations was used to detect the presence of the BCR/ ABL translocation characteristic of CML. The CD34+DR+ subpopulation contained BCR/ABL(+) cells in 11 of 12 marrow samples studied, whereas the CD34+DR- subpopulation contained BCR/ABL(+) cells in 6 of 9 CML marrow specimens. These cell populations were assayed for hematopoietic progenitor cells, and individual hematopoietic colonies were analyzed by PCR for their BCR/ABL status. Results from six patients showed that nearly half of the myeloid colonies cloned from CD34+DR- cells were BCR/ABL(+), although the CD34+DR- subpopulation contained significantly fewer BCR/ABL(+) progenitor cells than either low-density bone marrow (LDBM) or the CD34+DR+ fraction. These CD34+ cells were also used to establish stromal cell-free long-term bone marrow cultures to assess the BCR/ABL status of hematopoietic stem cells within these CML marrow populations. After 28 days in culture, three of five cultures initiated with CD34+DR- cells produced BCR/ABL(-) cells. By contrast, only one of eight cultures initiated with CD34+DR+ cells were BCR/ABL(-) after 28 days. These results indicate that the CD34+DR- subpopulation of CML marrow still contains leukemic progenitor cells, although to a lesser extent than either LDBM or CD34+DR+ cells.",
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