c-KIT exon 10 遺伝子変異陽性の t(8;21) を伴う急性骨髄性白血病の 1 例

Abstract

69 歳男性．胃びまん性大細胞 B 細胞リンパ腫（ diffuse large B cell lymphoma: DLBCL ）に対して R-CHOP 療法 6 コース実 施し寛解を維持していた．治療終了約 2 年後に末梢血中に芽球の出現を認めた．骨髄検査で芽球 15.6 %，白血病キメラ遺伝子 スクリーニングで RUNX1-RUNX1T1 遺伝子変異陽性を認め急性骨髄性白血病（ acute myeloid leukemia：AML ）と診断された． KIT 遺伝子変異解析では exon 10 p. Lys546= を認めた．daunorubicin（ DNR ）と cytosine arabinoside（ Ara-C ）による寛解 導入療法を施行し，完全寛解を獲得した．地固め療法として大量 Ara-C 療法を 3 コース行い治療を終了した．治療終了から 11ヶ 月後も再発なく経過している．RUNX1-RUNX1T1 遺伝子変異陽性急性骨髄性白血病における KIT 遺伝子変異は，exon 17 変異の 場合は予後不良とされるが，この症例での変異は exon 10 であったため，予後への影響は少ないと判断し，造血幹細胞移植を 施行せず，化学療法で治療を終了した．その妥当性の判断については議論が必要であるが，興味深い症例であり文献的考察を 加えて報告する．

A 69-year-old male diagnosed with gastric diffuse large B cell lymphoma (DLBCL) was in remission after receiving 6 cours es of R-CHOP therapy which consisted of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine and predinoso lone. Myeloblasts were detected in the peripheral blood approximately two years after the treatment. The results of the bone mar row examination revealed 15.6 % myeloblasts. Mutation of the RUNX1-RUNX1T1 gene was detected in the screening of chimeric genes related to leukemia and the patient was diagnosed with acute myeloid leukemia (AML). The KIT gene mutation analysis revealed the mutation exon 10p.lys546=. Remission induction therapy consisting of daunorubicin (DNR) and cytosine arabinoside (Ara-C) was conducted, and complete remission was achieved. Consolidation therapy consisting of three courses of large dose Ara-C therapy was conducted. At 11 months after the treatment, no recurrence was observed. Among the KIT gene mutations identified in AML with mutation in the RUNX1-RUNCX1T1 gene, the exon 17 mutation has a poor prognosis. However, since the mutation exon 10 found in the present case was considered to have little effect on the prognosis, we conducted chemotherapy without hematopoietic stem cell transplantation. Whether this decision was appropriate requires verification. Discussion with a review of the literature is given on this interesting case