Tags

Type your tag names separated by a space and hit enter

Leukemia cell lines: in vitro models for the study of Philadelphia chromosome-positive leukemia.
Leuk Res 1999; 23(3):207-15LR

Abstract

The Philadelphia (Ph) chromosome, the main product of the (9;22)(q34;q11) translocation, is the cytogenetic hallmark of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder of the hematopoietic stem cell; the Ph chromosome is also found in a sizeable portion of acute lymphoblastic leukemia (ALL) patients and in a small number of acute myeloid leukemia (AML) cases. At the molecular level, the t(9;22) leads to the fusion of the BCR gene (on chromosome 22) to the ABL gene (translocated from chromosome 9); this fusion gene BCR-ABL with its elevated tyrosine kinase activity must to be central to the pathogenesis of these disorders. Three different breakpoint cluster regions are discerned within the BCR gene on chromosome 22: M-bcr, m-bcr, and mu-bcr. Ph + leukemia cell lines are important tools in this research area. More than 20 ALL-and more than 40 CML-derived Ph + leukemia cell lines have been described. Furthermore, three Ph + B-lymphoblastoid cell lines, established from patients with Ph + ALL or CML, are available. Molecular analysis has documented BCR-ABL fusion genes in three apparently Ph chromosome-negative cell lines, all three derived from CML. Nearly all Ph + ALL cell lines have the m-bcr e1-a2 fusion gene (only two ALL cell lines have a b3-a2 fusion) whereas all CML cell lines, but one carry the M-bcr b2-a2, b3-a2 or both hybrids. The mu-bcr e19-a2 has been detected in one CML cell line. Four cell lines display a three-way translocation involving chromosomes 9, 22 and a third chromosome. Additional Ph chromosomes (up to five) have been found in four Ph + ALL cell lines and in 18 CML cell lines; though in some cell lines the extra Ph chromosome(s) might be caused by the polyploidy (tri- and tetraploidy) of the cells. Another modus to acquire additional copies of the BCR-ABL fusion gene is the formation of tandem repeats of the BCR-ABL hybrid as seen in CML cell line K-562. Both mechanisms, selective multiplication of the der(22) chromosome and tandem replication of the fusion gene BCR-ABL, presumably lead to enhanced levels of the fusion protein and its tyrosine kinase activity (genetic dosage effect). The availability of a panel of Ph + cell lines as highly informative leukemia models offers the unique opportunity to analyze the pathobiology of these malignancies and the role of the Ph chromosome in leukemogenesis.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Editorial
Review

Language

eng

PubMed ID

10071072

Citation

Drexler, H G., et al. "Leukemia Cell Lines: in Vitro Models for the Study of Philadelphia Chromosome-positive Leukemia." Leukemia Research, vol. 23, no. 3, 1999, pp. 207-15.
Drexler HG, MacLeod RA, Uphoff CC. Leukemia cell lines: in vitro models for the study of Philadelphia chromosome-positive leukemia. Leuk Res. 1999;23(3):207-15.
Drexler, H. G., MacLeod, R. A., & Uphoff, C. C. (1999). Leukemia cell lines: in vitro models for the study of Philadelphia chromosome-positive leukemia. Leukemia Research, 23(3), pp. 207-15.
Drexler HG, MacLeod RA, Uphoff CC. Leukemia Cell Lines: in Vitro Models for the Study of Philadelphia Chromosome-positive Leukemia. Leuk Res. 1999;23(3):207-15. PubMed PMID: 10071072.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Leukemia cell lines: in vitro models for the study of Philadelphia chromosome-positive leukemia. AU - Drexler,H G, AU - MacLeod,R A, AU - Uphoff,C C, PY - 1999/3/10/pubmed PY - 1999/3/10/medline PY - 1999/3/10/entrez SP - 207 EP - 15 JF - Leukemia research JO - Leuk. Res. VL - 23 IS - 3 N2 - The Philadelphia (Ph) chromosome, the main product of the (9;22)(q34;q11) translocation, is the cytogenetic hallmark of chronic myeloid leukemia (CML), a clonal myeloproliferative disorder of the hematopoietic stem cell; the Ph chromosome is also found in a sizeable portion of acute lymphoblastic leukemia (ALL) patients and in a small number of acute myeloid leukemia (AML) cases. At the molecular level, the t(9;22) leads to the fusion of the BCR gene (on chromosome 22) to the ABL gene (translocated from chromosome 9); this fusion gene BCR-ABL with its elevated tyrosine kinase activity must to be central to the pathogenesis of these disorders. Three different breakpoint cluster regions are discerned within the BCR gene on chromosome 22: M-bcr, m-bcr, and mu-bcr. Ph + leukemia cell lines are important tools in this research area. More than 20 ALL-and more than 40 CML-derived Ph + leukemia cell lines have been described. Furthermore, three Ph + B-lymphoblastoid cell lines, established from patients with Ph + ALL or CML, are available. Molecular analysis has documented BCR-ABL fusion genes in three apparently Ph chromosome-negative cell lines, all three derived from CML. Nearly all Ph + ALL cell lines have the m-bcr e1-a2 fusion gene (only two ALL cell lines have a b3-a2 fusion) whereas all CML cell lines, but one carry the M-bcr b2-a2, b3-a2 or both hybrids. The mu-bcr e19-a2 has been detected in one CML cell line. Four cell lines display a three-way translocation involving chromosomes 9, 22 and a third chromosome. Additional Ph chromosomes (up to five) have been found in four Ph + ALL cell lines and in 18 CML cell lines; though in some cell lines the extra Ph chromosome(s) might be caused by the polyploidy (tri- and tetraploidy) of the cells. Another modus to acquire additional copies of the BCR-ABL fusion gene is the formation of tandem repeats of the BCR-ABL hybrid as seen in CML cell line K-562. Both mechanisms, selective multiplication of the der(22) chromosome and tandem replication of the fusion gene BCR-ABL, presumably lead to enhanced levels of the fusion protein and its tyrosine kinase activity (genetic dosage effect). The availability of a panel of Ph + cell lines as highly informative leukemia models offers the unique opportunity to analyze the pathobiology of these malignancies and the role of the Ph chromosome in leukemogenesis. SN - 0145-2126 UR - https://www.unboundmedicine.com/medline/citation/10071072/Leukemia_cell_lines:_in_vitro_models_for_the_study_of_Philadelphia_chromosome_positive_leukemia_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0145212698001714 DB - PRIME DP - Unbound Medicine ER -