Comprehensive immunophenotypic study of acute myeloid leukemia with KMT2A (MLL) rearrangement in adults: A single‐institution experience

Abstract

Background 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. Methods 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. Results 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. Conclusion 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.

Trying to outRun‐DIC in KMT2Ar AML: It's tricky

“…More than 80 fusion partners have been described in KMT2Ar AML, of which t(9; 11) (p22.3; q23.3) is the most common KMT2A r in adults with AML 11 . Interestingly, Konoplev and colleagues identified five unique immunophenotypes in patients with KMT2Ar AML, including APL‐like (8%) 12 . Among those with APL‐like phenotype, t(9; 11) (p22; q23) was the most commonly observed karyotype with MLLT3 as the fusion partner.…”

“…11 Interestingly, Konoplev and colleagues identified five unique immunophenotypes in patients with KMT2Ar AML, including APL-like (8%). 12 Among those with APL-like phenotype, t(9; 11) (p22; q23) was the most commonly observed karyotype with MLLT3 as the fusion partner. Of note, Nguyen and colleagues did not detail the specific fusion partners in their patients with KMT2Ar AML; however, it would have been interesting to know if their findings correlated with cytogenetic abnormalities associated with APL-like phenotype in KMT2Ar AML.…”

MRD Monitoring in AML with KMT2A Gene Rearrangements: Comparison of Multiplex and Monoplex Real-Time RT-PCR Methods

“…Для острого промиелоцитарного лейкоза ПЦР на химерный транскрипт PML::RARa является «золотым стандартом» мониторинга МОБ [14]. Перестройки гена KMT2A также представляют собой привлекательную мишень для мониторинга МОБ на основе ПЦР, особенно в случаях зрелого моноцитарного фенотипа ОМЛ [15]. Однако стандартной системы для детекции перестроек гена KMT2A методом ПЦР на сегодняшний день не существует, поскольку они относительно редко that real-time monoplex RT-PCR is not only more specific, but also more sensitive for PCRbased MRD detection.…”

Issue Highlights—March 2022

“…Recent studies in the journal have characterized immunophenotypic features in myeloid neoplasms with mutated NPM1 (Zhou et al, 2019) and those associated with abnormalities of chromosome 7 (Chen et al, 2019). In the current issue, Konoplev et al describe the immunophenotypic features at diagnosis and relapse of 102 adults with AML with KMT2A rearrangement (Konoplev et al, 2022). In contrast with B‐lymphoblastic leukemia with KMT2A rearrangement, whose composite immunophenotype is fairly distinctive (Collins et al, 2021), the authors report an unexpected diversity of phenotypes in AML with KMT2A rearrangement—including cases with myeloblastic and acute promyelocytic‐like features, as well as a high frequency of immunophenotypic shifts at relapse (Konoplev et al, 2022).…”

“…In the current issue, Konoplev et al describe the immunophenotypic features at diagnosis and relapse of 102 adults with AML with KMT2A rearrangement (Konoplev et al, 2022). In contrast with B‐lymphoblastic leukemia with KMT2A rearrangement, whose composite immunophenotype is fairly distinctive (Collins et al, 2021), the authors report an unexpected diversity of phenotypes in AML with KMT2A rearrangement—including cases with myeloblastic and acute promyelocytic‐like features, as well as a high frequency of immunophenotypic shifts at relapse (Konoplev et al, 2022). Hafeez et al describe the first published case of a CD4+ T‐cell large granular lymphocytic leukemia (T‐LGLL) with mutated STAT3 (Hafeez et al, 2022).…”