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T-lymphoid/myeloid mixed phenotype acute leukemia and early T-cell precursor lymphoblastic leukemia similarities with NOTCH1 mutation as a good prognostic factor

Authors Noronha EP, Marques LVC, Andrade FG, Sardou-Cezar I, dos Santos-Bueno FV, Zampier CDP, Terra-Granado E, Pombo-de-Oliveira MS

Received 1 December 2018

Accepted for publication 6 March 2019

Published 2 May 2019 Volume 2019:11 Pages 3933—3943

DOI https://doi.org/10.2147/CMAR.S196574

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 4

Editor who approved publication: Dr Ahmet Emre Eskazan


Elda Pereira Noronha, Luísa Vieira Codeço Marques, Francianne Gomes Andrade, Ingrid Sardou-Cezar, Filipe Vicente dos Santos-Bueno, Carolina Da Paz Zampier, Eugênia Terra-Granado, Maria S Pombo-de-Oliveira

Paediatric Haematology-Oncology Program, Research Centre, Instituto Nacional de Câncer, Rio de Janeiro, RJ, Brazil

Purpose: T-lymphoid/Myeloid Mixed phenotype acute leukemia (T/M-MPAL) is ambiguous leukemia which overlaps with early T-cell precursor lymphoblastic leukemia (ETP-ALL). We have revisited the immunophenotyping profile of T/M-MPAL and ETP-ALL to identify differences and/or similarities, as these entities represent a therapeutic challenge in clinical practice.
Patients and methods: A total of 26 ETP-ALL and 10 T/M-MPAL cases were identified among 857 cases of childhood leukemia (T-ALL, n=266 and AML, n=591) before any treatment decisions. The variables analyzed were age strata, sex, clinical features, immunophenotyping, and molecular aberrations. Immunophenotyping was performed in all samples using a panel of cytoplasm and membrane antibodies to identify the lineage and blast differentiation. The mutational status of STIL-TAL1, TLX3, RUNX1, NOTCH1, FBXW7, FLT3, IL7R, RAS, KTM2A, and CDKN2A/B was tested using RT-PCR, FISH, and PCR sequencing methods. The outcomes were assessed in terms of overall survival (OS).
Results: The immunophenotypes were similar in ETP-ALL and T/M-MPAL, regarding the cellular expression of CD34, CD117, CD13/CD33, and CD11b, although CD2 and HLA-DR were more frequent in T/M-MPAL (p<0.01). aMPO positivity and myelomonocyte differentiation were definitive in separating both entities. NOTCH1, FLT3-ITD, and N/KRAS mutations as well as TLX3 and KMT2A rearrangements were found in both ETP-ALL and T/M-MPAL. Thirty-one patients received ALL protocol whereas five had AML therapy. The overall 5-year survival rate (pOS) was 56.4% for patients treated using ALL protocols. No differences were observed between T/M-MPAL (pOS of 57%) and ETP-ALL (pOS of 56%) patients. The prognostic value of NOTCH1mut, was associated with significantly better OS (pOS 90%) than NOTCH1wt, (pOS 37%) (p=0.017).
Conclusion: This research can potentially contribute to NOTCH1 as targeted therapy and prognostic assessment of T-cell mixed phenotype leukemia.

Keywords: T-lymphoid/myeloid mixed phenotype acute leukemia, early T-cell precursor lymphoblastic leukemia, NOTCH1 mutations

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