CD44 Expression Profile Varies According to Maturational Subtypes and Molecular Profiles of Pediatric T-Cell Lymphoblastic Leukemia

• Published in: Frontiers in oncology Vol. 8; p. 488
• Main Authors: Marques, Luísa Vieira Codeço, Noronha, Elda Pereira, Andrade, Francianne Gomes, Dos Santos-Bueno, Filipe Vicente, Mansur, Marcela B, Terra-Granado, Eugenia, Pombo-de-Oliveira, Maria S
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 31-10-2018
• Subjects: acute myeloid leukemia; CD44; CD44/CD44v6; NOTCH1; Oncology; T-cell leukemia; NOTCH1; T-cell leukemia; acute myeloid leukemia; CD44; CD44/CD44v6
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2018.00488

CD44 is a glycoprotein expressed in leucocytes and a marker of leukemia-initiating cells, being shown to be important in the pathogenesis of T cell acute lymphoblastic leukemia (T-ALL). In this study, we have (i) identified the aberrant antigenic pattern of CD44 and its isoform CD44v6 in T-ALL; (ii) tested the association with different T-cell subtypes and genomic alterations; (iii) identified the impact of CD44 status in T-ALL outcome. Samples from 184 patients (123 T-ALL and 61 AML; <19 years) were analyzed throughout multiparametric flow cytometry. Mutations in
as well as
and
rearrangements were detected using standard molecular techniques. CD44 expression was characterized in all T-ALL and AML cases. Compared with AML samples in which the median fluorescence intensity (MFI) was 79.1 (1-1272), T-ALL was relatively low, with MFI 43.2 (1.9-1239); CD44v6 expression was rarely found, MFI 1 (0.3-3.7). T-ALL immature subtypes (mCD3/CD1a
) had a lower CD44 expression, MFI 57.5 (2.7-866.3), whereas mCD3/TCRγδ
cases had higher expressions, MFI 99.9 (16.4-866.3).
and
were associated with low CD44 expression, whereas
and
cases had intermediate expression. In relation to clinical features, CD44 expression was associated with tumor infiltrations (
= 0.065). However, no association was found with initial treatment responses and overall survival prediction. Our results indicate that CD44 is aberrantly expressed in T-ALL being influenced by different genomic alterations. Unraveling this intricate mechanism is required to place CD44 as a therapeutic target in T-ALL.