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.
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 JH and Jk 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.
Higa
T
T
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Okabe
M
M
Kunieda
Y
Y
Kodama
S
S
Itaya
T
T
Kurosawa
M
M
Sakurada
K
K
Maekawa
I
I
Shoji
M
M
Kasai
M
M
D000368:Aged; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002454:Cell Differentiation; D002460:Cell Line; D046508:Culture Techniques / Q000379:methods; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis*; D015870:Gene Expression; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006801:Humans; D007621:Karyotyping; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D015513:Oncogene Proteins / Q000235:genetics*; D009857:Oncogenes; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction / Q000379:methods; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000473:pathology*; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D012334:RNA, Neoplasm / Q000032:analysis; D015183:Restriction Mapping; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D004273:DNA, Neoplasm; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D012334:RNA, Neoplasm; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr