Konoplev Sergej, Wang Xiaoqiong, Tang Guilin, Li Shaoying, Wang Wei, Xu Jie, Pierce Sherry A, Jia Fuli, Jorgensen Jeffrey L, Ravandi Farhad, Issa Ghayas C, Medeiros L Jeffrey, Wang Sa A
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Cytometry B Clin Cytom. 2022 Mar;102(2):123-133. doi: 10.1002/cyto.b.22051. Epub 2021 Dec 28.
Acute myeloid leukemia (AML) with KMT2A (MLL) rearrangement is known for monocytic or myelomonocytic differentiation, but the full immunophenotypic spectrum and dynamic changes of the immunophenotype in this genetically defined disease have not been systematically studied.
We reviewed the immunophenotype, karyotype, and mutations at the time of initial diagnosis and relapse of adults with AML with KMT2A rearrangement in our institution between 2007 and 2020.
We identified 102 patients: 44 men and 58 women with a median age of 52 years (range, 18-87). Forty-three patients were considered to be therapy-related. Twenty-four out of 64 patients relapsed from complete remission after induction therapy, 34 had persistent/progressive disease, and 58 patients died with a median overall survival of 17 months. We detected five immunophenotypes: immature monocytic (38%); myelomonocytic (22%); myeloblastic (22%); mature monocytic (10%); and acute promyelocytic (APL)-like (8%). By chromosomal breakpoints, we presumed 11 different partners; t(9;11) (p22;q23)/MLLT3-KMT2A was the most common rearrangement (n = 56, 55%), followed by t(6;11) (q27;q23)/AFDN-KMT2A (n = 13,13%). Patients with t(6;11) (q27;q23)/AFDN-KMT2A preferentially showed a myeloblastic phenotype (p = 0.026). Mutations were detected in 39/64 (61%) cases, and RAS pathway (NRAS/KRAS/PTPN11) was involved in 26/64 (41%) cases. None of the APL-like cases had mutations detected. At the time of disease relapse, 10/24 (42%) showed major immunophenotypic change, and 7/10 cases gained additional cytogenetic and/or molecular alterations.
The immunophenotype of AML with KMT2A rearrangement is more diverse than previously recognized, with a substantial subset showing no evidence of monocytic differentiation. Major immunophenotype change is common at the time of relapse.
伴有KMT2A（MLL）重排的急性髓系白血病（AML）以单核细胞或粒单核细胞分化为特征，但在这种基因定义的疾病中，完整的免疫表型谱以及免疫表型的动态变化尚未得到系统研究。
我们回顾了2007年至2020年间在我们机构确诊并复发的伴有KMT2A重排的成年AML患者初次诊断和复发时的免疫表型、核型及突变情况。
我们共纳入102例患者，其中男性44例，女性58例，中位年龄52岁（范围18 - 87岁）。43例患者被认为与治疗相关。64例患者中，24例在诱导治疗后从完全缓解状态复发，34例病情持续/进展，58例患者死亡，中位总生存期为17个月。我们检测到五种免疫表型：未成熟单核细胞型（38%）；粒单核细胞型（22%）；原始粒细胞型（22%）；成熟单核细胞型（10%）；急性早幼粒细胞白血病（APL）样型（8%）。根据染色体断点，我们推测有11种不同的伙伴基因；t(9;11)(p22;q23)/MLLT3 - KMT2A是最常见的重排类型（n = 56，55%），其次是t(6;11)(q27;q23)/AFDN - KMT2A（n = 13，13%）。伴有t(6;11)(q27;q23)/AFDN - KMT2A的患者优先表现为原始粒细胞表型（p = 0.026）。64例患者中有39例（61%）检测到突变，26例（41%）涉及RAS通路（NRAS/KRAS/PTPN11）。APL样型病例均未检测到突变。在疾病复发时，24例中有10例（42%）出现主要免疫表型改变，其中7例获得了额外的细胞遗传学和/或分子改变。
伴有KMT2A重排的AML免疫表型比之前认识到的更多样化，相当一部分患者没有单核细胞分化的证据。复发时主要免疫表型改变很常见。
