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

Abstract

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 NOTCH1 mut was associated with significantly better OS (pOS 90%) than NOTCH1 wt (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.

The Profile of Immunophenotype and Genotype Aberrations in Subsets of Pediatric T-Cell Acute Lymphoblastic Leukemia

“…In contrast, the ETP-ALL had a 5-year pOS of 56.7%. Recently we demonstrated that ETP-ALL with NOTCH1 mut was associated with significantly better pOS (90%) than NOTCH1 wt (pOS 37%; p = 0.017) (44). Interestingly, although the early cortical subtype had higher frequencies of NOTCH1 mut , it presented a relatively low pOS (48.6%).…”

Immature acute leukaemias: lessons from the haematopoietic roadmap

“…This article is protected by copyright. All rights reserved cases [17,30,37,39,40,42,43,51,[56][57][58][59][60][61]. This is in contrast to patterns of signalling alteration seen in more phenotypically mature leukaemias.…”

Transcriptional Regulation of Genes by Ikaros Tumor Suppressor in Acute Lymphoblastic Leukemia

“…IL7R is responsible for the differentiation of hematopoietic cells into lymphoid progenitor cells, and its level is altered during the development of T-and B-cells [113,114]. The IL7R gene encoding the IL7R-α chain heterodimerizes with the IL7R-γ form or with the cytokine receptor-like factor 2 (CRLF2) to form IL7 receptor or thymic stromal lymphopoietin (TSLP) receptor, respectively [115][116][117].…”