KBM-7, a human myeloid leukemia cell line with double Philadelphia chromosomes lacking normal c-ABL and BCR...

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• The KBM-7 cell line originates from a patient with chronic myeloid leukemia (CML) in the blastic phase.
• Characterization of KBM-7 includes morphology, immunophenotype, cytogenetics, and proliferative capacity.
• The cell line was developed without exogenous lymphokines, showing decreased cloning capacity with added colony-stimulating factors.

Purpose of the Study:

• To characterize the KBM-7 cell line for its utility in CML research.
• To investigate the molecular events in neoplastic transformation in CML.
• To study the effects of BCR-ABL and ABL-BCR on CML cell proliferation.

Main Methods:

• Morphological, immunophenotypic, cytogenetic, and proliferative capacity assessments.
• Molecular characterization of the BCR-ABL breakpoint and gene expression using reverse-transcriptase polymerase chain reaction.
• Heterotransplantation of KBM-7 cells into nude mice.

Main Results:

• KBM-7 cells display an aberrant immature myeloid phenotype with a doubling time of 22 hours and high cloning efficiency.
• Early passages showed near-haploid and hyperdiploid stem lines, with the latter becoming predominant, averaging 49 chromosomes.
• Passage 89 cells possessed two Philadelphia chromosomes [t(9;22)(q34;q11)], lacking normal copies of chromosomes 9 and 22, with BCR 2/ABL II splice junction and high p210BCR-ABL activity.
• Heterotransplantation into nude mice resulted in granulocytic sarcomas, locally invasive but non-metastatic.

Conclusions:

• The KBM-7 cell line is a valuable tool for investigating molecular mechanisms of neoplastic transformation in CML.
• It allows for the study of BCR-ABL and ABL-BCR effects on CML cell proliferation in the absence of normal BCR and c-ABL expression.
• The cell line's ability to form tumors in vivo further supports its utility in CML research.