ABL1 Gene Amplification and Aberration Involving HOX11L2/TLX3 in T-Acute Lymphoblastic Leukemia (T-ALL).
Authors: Luño Elisa , Sanzo Carmen , Jonte Fermin , LLorente Regina , Fanjul Emilia , Gonzalez Soledad , Martínez Araceli 
Published: October 2019

Abstract
Background and objective: T-ALL accounts for approximately 15% of childhood ALL and 25% adult ALL. Cytogenetic abnormalities are less frequently detect in T than B-ALL. The most frequent genetic alterations include 7q32, 14q11 or 1p32 (TAL1) rearrangements, and deletions 6q, 9p, 5q, 11q, 12p, 7q,and 13q. Novel cryptic translocation was described: t(5;14) involving HOX11L2 gen. ABL1 amplification has been detected in 5% T-ALL carry a cryptic NUP214-ABL1 fusion. In our study conventional cytogenetic analysis were complemented by fluorescence in situ hybridization (FISH) to improve detection chromosomal abnormalities in T-ALL. Split-signal dual color TLX3, SIL-TAL, MLL probes and LSI BCR/ABL extra signal dual color were used.
Results: 108 patients with ALL, 17 (15,7%) of these patients had T-ALL.13 (76,5%) males and four females. Median age was 19 years (3–55 years) and seven (41,2%) were < 15 years. FAB subtypes:13 ALL1 and 4 ALL2. One patient was classified as showing stage thymocyte development, five were classified as stage II and seven as stage III. 5/17 (29,4%) co-expressed myeloid markers (CD13 or CD33). Median hemoglobin was 101 g/L, leukocytes 80,9×109/L, platelets 80×109/L, blood blasts 90%, bone marrow blasts 95%, LDH 1008,5 UL (8/17 had >1000 UL, normal value <460 UL). Eight patients (47,5%) had leukocytosis >50×109/L and 10/17 (58,8%) presented marked hepato-splenomegaly and lymphadenopathy. One patient presented SNC infiltration. 13/17 (76,4%) had a successful cytogenetic study and seven of these (53,8%) with clonal chromosomal abnormalities: two del (12p), one del (9p), one del (7q) (deletion 11q associated), one t(11;14), one monosomy 21 and one hiperdiploid karyotype (>50 chromosomes). FISH analysis was preformed in 12 cases. None aberration involving TAL1 gene have been detect. MLL rearrangement was detect in the patient del(7q) and del (11q) associated. Other patient presented aberration involving HOX11L2/TLX3 and ABL amplification (>20 ABL signals and two BCR signals) with poor quality of metaphases. This patient was a male 4 years old, diagnosed T-ALL1 (stage III Egil).He had hepato-esplenomegaly, mediastinal mass, the most leukocyte count (492×109/L) and high LDH (4553 UL). The blasts expressed CD45, CD4, CD7, CD2, CD5, CD4, CD8, CD10, CD1, CD38 and cCD3. He received treatment with Pethema ALL-96 intermediate risk protocol and bone marrow study on day 14 didn’t present blast, he achieved complete remission on day 35 (EMR <0.01 and cytogenetic remission) and he is alive (follow-up 1,6 months). In this serie, all patients received treatment with chemotherapy risk adapted protocol, 16/17 achieved complete remission but 9/16(52,9%) relapsed (with normal karyotype 33,3%; with abnormal karyotype 75%) Median overall and disease free survival was 28.5 and 86,6 months respectively (probability of relapse 45,7% at 3 years). ABL amplification is a rare event in T-ALL (5,8% in this series). Our case present translocation HOX11l2/TLX3 asociated. The expression of CD1,CD10, and CD3 is more frequent in patient with translocation or expression HOX11L2 gene as our patient.