Aberrant leukemia-associated immunophenotype as potential harbinger of lineage switch in <i>KMT2A</i>-rearranged leukemia: a case series

Yost, Christine M.; Gaikwad, Amos; Parsons, D. Williams; Rabin, Karen R.; Gant, Vincent U.; Fisher, Kevin E.; Marcogliese, Andrea N.; Schafer, Eric S.

doi:10.1080/10428194.2020.1815018

Cited by 3 publications

(2 citation statements)

References 15 publications

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“…KMT2A ‐rearranged AML is an aggressive subtype of AML with frequent monocytic or myelomonocytic differentiation, and some cases can present with lineage switch to acute lymphoblastic leukemia (Rossi et al, 2012; Yost et al, 2020). In our experience, the immunophenotype of KMT2A ‐rearranged AML is diverse; some cases show a monocytic or monoblastic immunophenotype, and other cases have a myeloblastic or myelomonocytic immunophenotype.…”

Section: Discussionmentioning

confidence: 99%

Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry

Fang

Wang

et al. 2022

Cytometry Part B Clinical

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Background: Prompt diagnosis of acute promyelocytic leukemia (APL) is critical for patient care. In this study, we aimed to characterize the immunophenotype of APL and explore immunophenotypic difference between APL and its mimics using flow cytometric analysis.Methods: Eighty-five cases were collected, including 47 APL, 26 NPM1-mutated acute myeloid leukemia (AML) and 12 KMT2A-rearranged AML with an APL-like immunophenotype. Immunophenotypes were analyzed using flow cytometric analysis. Results: APL showed four distinct patterns (designated a-d) based on CD45/SSC plots. Blasts in patterns a-c showed high side scatter, whereas blasts in pattern d had low side scatter and were located in the traditional blast gate. Compared with patterns a-c, pattern d of APL (APL-D) was more often positive for CD2 (p = 0.0005) and CD34 (p = 0.0002) in blasts. All NPM1-mutated AML and KMT2Arearranged AML cases with an APL-like immunophenotype had blasts in the traditional blast gate on CD45/SSC, mimicking APL-D. In comparison, uniform CD13 and positive CD64 were seen in 100% (n = 13) APL-D cases and in only 2 of 26 (8%) NPM1-mutated AML cases (p < 0.0001). In addition, APL-D cases were more likely to be positive for CD2 and/or CD34 than NPM1-mutated AML (p < 0.0001 and p = 0.0007, respectively). In comparison with APL-D, KMT2Arearranged AML cases were less often positive for myeloperoxidase (MPO) (p = 0.001), with none being strongly positive. Similar to NPM1-mutated AML and different from APL-D, KMT2A-rearranged AML cases were rarely positive for CD34 and all negative for CD2.Conclusions: APL and its immunophenotypic mimics share some immunophenotypic similarities but can be distinguished by CD2, CD13, CD34, CD64, and MPO.

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Section: Discussionmentioning

confidence: 99%

Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry

Fang

Wang

et al. 2022

Cytometry Part B Clinical

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“…However, in our practice, we have observed a more diverse immunophenotype in cases of AML with KMT2A rearrangement, including a proportion of cases with a non‐monocytic phenotype. Furthermore, AML with KMT2A rearrangement has been known for its immunophenotypic/lineage plasticity, and it is one of the most frequent subtypes of acute leukemia with lineage switch post‐therapy (Rossi et al, 2012; Yost et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

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

Konoplev

Wang

Tang

et al. 2021

Cytometry Part B Clinical

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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.

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Lineage switch from acute myeloid leukemia to acute lymphoblastic leukemia

Zong

Xie

Kong

et al. 2022

Leukemia & Lymphoma

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Aberrant leukemia-associated immunophenotype as potential harbinger of lineage switch in KMT2A-rearranged leukemia: a case series

Cited by 3 publications

References 15 publications

Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry

Acute promyelocytic leukemia: Immunophenotype and differential diagnosis by flow cytometry

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

Lineage switch from acute myeloid leukemia to acute lymphoblastic leukemia

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