Bibliographic Details
| Title: |
FLT3-ITD in Children with Early T-cell Precursor (ETP) Acute Lymphoblastic Leukemia: Incidence and Potential Target for Monitoring Minimal Residual Disease (MRD). |
| Authors: |
Lo Nigro, Luca, Andriano, Nellina, Buldini, Barbara, Silvestri, Daniela, Villa, Tiziana, Locatelli, Franco, Parasole, Rosanna, Barisone, Elena, Testi, Anna Maria, Biondi, Andrea, Valsecchi, Maria Grazia, Rizzari, Carmelo, Conter, Valentino, Basso, Giuseppe, Cazzaniga, Giovanni |
| Source: |
Cancers; May2022, Vol. 14 Issue 10, p2475-N.PAG, 9p |
| Subject Terms: |
GENETIC mutation, LYMPHOBLASTIC leukemia, RETROSPECTIVE studies, T cells, HEMATOPOIETIC stem cell transplantation, DISEASE remission |
| Abstract: |
Simple Summary: The prevalence of FLT3-ITD among children with ETP-ALL must be determined. MRD monitoring in ETPs is hampered by the lack of Immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements. We determined the incidence of FLT3-ITD among children with ETP and performed MRD monitoring using FLT3-ITD sequences, successfully testing a new method of MRD detection. Moreover, we highlighted that the FLT3 pathway could represent a therapeutic target for precision therapy in patients with ETP. Early T-cell precursor (ETP) is an aggressive form of acute lymphoblastic leukemia (ALL), associated with high risk of relapse. This leukemia subtype shows a higher prevalence of mutations, typically associated with acute myeloid leukemia (AML), including RAS and FLT3 mutations. FLT3-ITD was identified in 35% cases of adult ETP-ALL, but data in the pediatric counterpart are lacking. ETPs frequently lack immunoglobulin (IG) and T-cell receptor (TR) gene rearrangements, used for minimal residual disease (MRD) monitoring. Among 718 T-ALL enrolled in Italy into AIEOP-BFM-ALL2000, AIEOP-ALLR2006, and AIEOP-BFM-ALL2009 consecutive protocols, 86 patients (12%) were identified as ETP and 77 out of 86 children were studied for the presence of FLT3-ITD. A total of 10 out of 77 (13%) ETP cases were FLT3-ITD positive. IG/TR MRD monitoring was feasible only in four cases. FLT3-ITD MRD monitoring was performed using real-time PCR in all FLT3-ITD positive ETP cases. A comparison between IG/TR and FLT3-ITD resulted in comparable findings. Our study demonstrated that the FLT3-ITD prevalence in children was lower (13%) than that reported in adult ETP-ALL. FLT3-ITD can be used as a marker for sensitive molecular MRD monitoring in ETP-ALL when IG/TR markers are not available, potentially selecting those patients who should spare allogeneic hematopoietic stem cell transplantation (HSCT). Finally, the FLT3 pathway is a robust druggable target in this aggressive form of leukemia. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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