| Project/Area Number |
07670836
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
IMAIZUMI Masue Department of Pediatrics, Tohoku University School of Medicine, Assistant Professor, 医学部, 講師 (40191895)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Hoshiro Dept. of Pediatrics, Tohoku Univ. School of Medicine, Clinical Instructor, 医学部・附属病院, 医員
IDE Hiroyuki Dept. of Biology, Molecular and cell Biology Division, Tohoku Univ. School of Sc, 理学部, 教授 (70022704)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1995: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | APL / ATRA / Differentiation / PML / RARalpha / apoptosis / RT-PCR |
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| Research Abstract |
(1) We investigated the evidence of apoptosis during all-trans retinoic acid (ATRA) therapy in three patients with acute promyelocytic leukemia (APL). Blood cells derived from the patients in vivo showed DNA fragmentation transitionally in the phase of regression of hyperleukocytosis, the majority of which were mature yet aberrant granulocytes of APL clone origin. Furthermore, morphological features of apoptosis were also demonstrated in a small fraction of cells simultaneously with the appearance of DNA fragmentation in two patients who received adjunctive chemotherapy in addition to ATRA therapy. These findings suggest that APL cells, even if in a small fraction, may undergo apoptosis while differentiating in vivo with ATRA therapy, and that rapid clearance of leukemic cells from the patient's blood may be attributed to apoptotic cell death of APL cells.
(2) We studied the disease monitoring of nine patients with APL by detecting PML/RARalpha mRNA fusion points using RT-PCR combined with ASO.Patients (four males and five females) were 8.3 years of mean age (a range from four to fifteen years old) with an average observation period of 30 months (a range from 18 to 52 months). After obtaining complete remission with ATRA therapy, six patients received multidrug-combined chemotherapy (group A), in whom bone marrow transplantation (BMT) was performed later in three patients during first remission and in one after BM relapse. The rest of three patients received an alternatively combined therapy with chemotherapeutic agents and ATRA (group B), from whom one relapsed and died in refractory state. This method of disease monitoring could identified a high risk of one patient in group A who showed a shift of MRD positivity from nested to single PCR levels, however, it was not informative for another in group B who relapse at fifteen months from onset.
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