1993 Fiscal Year Final Research Report Summary
Analysis of the mechanism of retinoic acid-induced differentiation of acute promyelocytic leukemia
| Project/Area Number |
04807065
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Pediatrics
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
IMAIZUMI Mashue Tohoku University School of Medicine, Departement of Pediatrics, Assistant Professor, 医学部・附属病院, 講師 (40191895)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
小泉 善嗣 東北大学, 医学部・附属病院, 助手 (90250761)
IDE H. Tohoku University Biological Institute Professor, 理学部, 教授 (70022704)
KOIZUMI Y. Tohoku University School of Medicine, Departement of Pediatrics, Instructor
|
|---|
| Project Period (FY) |
1992 – 1993
|
| Keywords | Acute promyelocytic Leukemia / retinoic acid / PML / RAR chimeric gene / Induction of differentiation |
|---|
| Research Abstract |
(A)The effects of G-CSF or GM-CSF on ATR-induced differentiation of APL.
All-trans retinoic acid(ATRA)induces differentiation of acute promyelocytic leukemia(APL), but the effect of cytokines regulating myeloid differentiation on ATRA-induced APL cells is poorly understood. In this study, maturation and proliferation of fresh APL cells were examined when induced in vitro by granulocyte or granulocyte/macrophage colony-stimulating factors(G-CSF or GM-CSF)in combination of ATRA.APL cells showed a low proliferating activity when induced by ATRA alone. In contrast, cells induced by G-CSF or GM-CSF alone showed increased DNA syntheses, the levels of which were not significantly affected by the combination of ATRA with CSFs. Interestingly, G-CSF or GM-CSF poteniated the capability of ATRA-induced cells to reduce nitroblue tetrazolium(NBT), while G-CSF or GM-CSF alone induced no NBT reduction. Furthermore, if not all patients APL cells induced by ATRA with G-CSF showed an increased activity of
… More
chemotaxis and CD11a expression. These findings suggest that G-CSF or GM-CSF can potentiate differentiation of ATRA-induced APL cells while stimulating their proliferating activity as well, and that G-CSF, rather than GM-CSF, may be a useful adjunct to promote ATRA-induced differentiation of APL.
(B)Detection and analysis of PML/RARa chimeric mRNA in APL.
The translocation t(15 ; 17), a cytogenetic abnomality specific for acute promyelocytic leukemia(APL), generates a rearrangement between a PML gene and a retinoic acid receptor-a(RARa)gene. In this study, PML/RARa chimeric transcripts and fusion points in ten patients with APL was analyzed by a reverse transcripitase-polymerase chain reaction(RT-PCR)and an allele specific oligonucleotide(ASO)hybridization. PML/RARa mRNA was detected in all patients, and PML exon at fusion points was various in patients, while RARa exon was exclusively exon 3. ASO hybridization and DNA sequencing revealed different fusion patterns ; PML(exon3)/RARa(exon3)in two, PML(exon4)/RARa(exon3)in one, or PML(exon6)/RARa(exone3)in seven out of ten patients, respectively. Less
|
