Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins

• Published in: Blood cancer journal (New York) Vol. 12; no. 1; p. 14
• Main Authors: Steimlé, Thomas, Dourthe, Marie-Emilie, Alcantara, Marion, Touzart, Aurore, Simonin, Mathieu, Mondesir, Johanna, Lhermitte, Ludovic, Bond, Jonathan, Graux, Carlos, Grardel, Nathalie, Cayuela, Jean-Michel, Arnoux, Isabelle, Gandemer, Virginie, Balsat, Marie, Vey, Norbert, Macintyre, Elizabeth, Ifrah, Norbert, Dombret, Hervé, Petit, Arnaud, Baruchel, André, Ruminy, Philippe, Boissel, Nicolas, Asnafi, Vahid
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 26-01-2022; Springer Nature B.V; Nature Publishing Group
• Subjects: 45/22; 45/23; 45/77; 45/90; 631/208/68; 631/67/1990/283/2125; Adolescent; Adult; Biomedical and Life Sciences; Biomedicine; Cancer Research; Child; Child, Preschool; Female; Hematology; Human health and pathology; Humans; Infant; Leukemia; Life Sciences; Male; Middle Aged; Oncogene Proteins, Fusion - genetics; Oncology; Pediatrics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - diagnosis; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - pathology; Prognosis; T-Lymphocytes - pathology; Young Adult
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/s41408-022-00613-9

T-cell acute lymphoblastic leukemias (T-ALL) represent 15% of pediatric and 25% of adult ALL. Since they have a particularly poor outcome in relapsed/refractory cases, identifying prognosis factors at diagnosis is crucial to adapting treatment for high-risk patients. Unlike acute myeloid leukemia and BCP ALL, chromosomal rearrangements leading to chimeric fusion-proteins with strong prognosis impact are sparsely reported in T-ALL. To address this issue an RT-MPLA assay was applied to a consecutive series of 522 adult and pediatric T-ALLs and identified a fusion transcript in 20% of cases.
PICALM-MLLT10
(4%,
n
 = 23),
NUP214-ABL1
(3%,
n
 = 19) and
SET-NUP214
(3%,
n
 = 18) were the most frequent. The clinico-biological characteristics linked to fusion transcripts in a subset of 235 patients (138 adults in the GRAALL2003/05 trials and 97 children from the FRALLE2000 trial) were analyzed to identify their prognosis impact. Patients with HOXA trans-deregulated T-ALLs with MLLT10, KMT2A and SET fusion transcripts (17%, 39/235) had a worse prognosis with a 5-year EFS of 35.7% vs 63.7% (HR = 1.63;
p
 = 0.04) and a trend for a higher cumulative incidence of relapse (5-year CIR = 45.7% vs 25.2%, HR = 1.6;
p
 = 0.11). Fusion transcripts status in T-ALL can be robustly identified by RT-MLPA, facilitating risk adapted treatment strategies for high-risk patients.