評探討t(8;21)(q22;q22)-AML M2 (FAB)病人之細胞遺傳學變異與免疫分型的異對治療及預後影響

Exploring the Impact of Cytogenetic Abnormality and Aberrant Immunophenotyping on the Treatment and Prognosis of AML Patients with t(8;21)(q22;q22)

t（8;21）（q22;q22）染色體突變常出現於急性骨髓性白血病French-American-British （FAB）分類中的M2型，屬於預後較好的突變型，然而，仍有約三到四成患者會復發。為了探討其他染色體或基因突變、及骨髓細胞免疫分型特徵對其預後影響，我們整理35位t（8;21）（q22;q22）-AML M2案例資料，發現帶有至少三種不同染色體突變的複雜染色體病人，其總體死亡率有較高的趨勢（33% v.s. 17%, HR=2.96, p=0.1652）；合併有c-KIT基因突變的案例整體存活率明顯較低（c-KITmut: 58%, v.s. c-KITwt: 91%, p=0.0358），若合併c-KIT突變且骨髓細胞表現CD56者，移植後RUNX1-RUNX1T1融合基因表現量維持較高（與初診斷時相比的下降比率平均值分別為c-KITmut/CD56+: -3.77;非c-KITmut/CD56-: -4.50）。因此，在診斷初期，建議針對染色體核型、c-KIT基因、CD56抗原表現特別評估，辨別其預後風險，以考慮更積極的治療方式，以降低病人復發率、提高存活率。

Acute myeloid leukemia (AML) with t(8;21)(q22;q22); RUNX1-RUNX1T1 is generally associated with favorable prognosis. However, the outcome is heterogeneous, and approximately 30%–40% of patients with t(8;21)(q22;q22)-positive AML relapse after standard treatment. In the present study, we analyzed 35 patients with newly diagnosed t(8;21)(q22;q22)-AML-M2 (French-American-British [FAB] classification) to explore the prognostic effects of the cytogenetic abnormality and aberrant immunophenotype. In our cohort, patients with a complex karyotype (CK) had a higher mortality rate (33%) than did those without CK (17%; hazard ratio: 2.96, p = 0.1652). In addition, overall survival (OS) was considerably lower in the patients with additional c-KIT mutation (c-KITmut: 58%) than in those without (c-KITwt: 91%, p = 0.0358). The RUNX1-RUNX1T1 log reduction ratio might be associated with poor outcomes after allogeneic hematopoietic stem cell transplantation in patients with c-KIT mutation combined with aberrant CD56 expression (mean of the RUNX1-RUNX1T1 log reduction ratio: c-KITmut/CD56+: -3.77; non-c-KITmut/CD56-: -4.50). Karyotypes, the c-KIT mutant, and CD56 expression levels in the bone marrow of patients with t(8;21)(q22;q22)-AML-M2 should be investigated because of their potential prognostic significance.