Establishment and Characterization of a New Ph¹-Positive ALL Cell Line (ALL/MIK) Presenting bcr Gene Rearrangement on bcr-2 and ALL-Type bcr/abl Transcript: Suggestion of in vitro Differentiation to Monocytoid Lineage

Abstract

A new Ph¹-positive acute lymphoblastic leukemia cell line, designated as ALL/MIK, has been developed from a patient with Ph¹-positive acute leukemia. The ALL/MIK cells showed an immunophenotype of common ALL with rearranged J_H and J_k genes. The ALL/MIK cells showed no M-bcr rearrangement using Southern blot analysis with either 3′ or 5′ M-bcr probes, but had the bcr gene rearrangement on bcr-2 within the first intron of the bcr gene. Consistent with this result, the reverse transcriptase-dependent polymerase chain reaction (RT-PCR) assay revealed that the ALL/MIK cells contained the transcript derived fusion of the first exon of bcr gene and the second exon of abl gene. Although the ALL/MIK cells were defined as early pre-B cells by immunophenotypical and genotypical analyses, they were capable of differentiating into monocytoid lineage by when cultured with TPA. Furthermore, another Ph¹-positive ALL cell line, (TOM-1), was investigated for its ability to differentiate to monocytoid lineage. TOM-1 was also induced to monocytoid lineage by TPA. Thus, the present study suggested that the leukemic transformation in some Ph¹-positive ALL may occur at the level of multipotential hematopoietic cells capable of differentiating towards lymphoid and myelo-monocytoid lineage.

Key Words:

• Ph¹-positive ALL
• bcr-2
• TPA
• pre-B cell
• monocytoid differentiation