Phenotypic and genetic characterization of adult T-cell acute lymphoblastic leukemia with del(9)(q34);SET-NUP214 rearrangement

Abstract

SET-NUP214 rearrangement is a recently recognized recurrent chromosomal translocation mostly observed in T-ALL. In order to characterize this rare entity, we performed phenotypic and genetic characterization of SET-NUP214 rearrangement through an investigation of a series of 40 consecutive samples of adult T-ALL that was selected among 229 adult ALL cases during 4 years in a single institution. Four cases (10%) of SET-NUP214 translocation were identified in our study. In all cases, diagnosis of T-ALL was established according to the World Health Organization (WHO) classification, and clonal TCR rearrangements were found. The immunophenotypic markers were indicative of the precursor nature of T lymphoblasts, and they expressed one or both of the myeloid-associated antigens (CD13, CD33). Conventional cytogenetic analysis revealed complex chromosomal aberrations in all four SET-NUP214 rearranged cases and del(12)(p13)/ETV6 was frequently involved. Array-CGH demonstrated additional genomic imbalances in addition to deletion 9q34. The genomic breakpoint sequencing identified breakpoints at SET intron 7 and NUP214 intron 17, and random nucleotide addition was found in two cases at the site of rearrangement. Our independently derived data set from a single institution confirms previous findings of SET-NUP214 rearrangement, indicates the relatively high incidence of SET-NUP214 rearrangement in adult T-ALLs, and also demonstrates comprehensive clinical, phenotypic, and genetic characteristics of this entity. Also, our report on genomic breakpoints demonstrates the homogeneity in the localization of the genomic breakpoints at 9q34. Concurrent chromosomal aberrations identified in this study should provide further areas of interest in investigation of SET-NUP214-mediated leukemogenesis.

B-cell acute lymphoblastic leukemia associated with SET-NUP214 rearrangement: A case report and review of the literature

“…The majority of these patients experienced T-ALL (38/42; 90.4%), while other subtypes of leukemia accounted for <10%, including AUL (4.8%), AML (2.4%) and B-ALL (2.4%). Ben Abdelali et al (12) reported an incidence of SET-NUP214 of ~5.6% among 196 patients with T-ALL, which was slightly lower than that reported by previous studies in China and Korea concerning 59 (10.3%) and 40 (10.0%) patients with T-ALL, respectively (8,10). According to previous studies, the incidence of SET-NUP214 among patients with T-ALL appears to be ~3.0-10.3% (3,4,7,8,10,12).…”

“…The SET-NUP214 fusion gene has been previously reported in T-ALL, but rarely in AML and AUL (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). However, it has not been be reported thus far in B-ALL.…”

“…Cryptic t(9;9)(q34;q34) and del(9)(q34.11q34.13) are rare genetic abnormalities that lead to the formation of the SET nuclear proto-oncogene (SET)-nucleoporin (NUP)214 fusion gene, which is a marker of acute leukemia (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). SET-NUP214 was first detected in a patient with acute undifferentiated leukemia (AUL) (1), and later detected in two patients with acute myeloid leukemia (AML) (2,5).…”

“…SET-NUP214 was first detected in a patient with acute undifferentiated leukemia (AUL) (1), and later detected in two patients with acute myeloid leukemia (AML) (2,5). Recent increasing evidence supports an association between SET-NUP214 and pediatric and adult T-cell acute lymphoblastic leukemia (T-ALL) with a frequency of ~3.3-10.3% (3,4,(6)(7)(8)(9)(10)(11)(12). Gorello et al (4) reported an estimated incidence of SET-NUP214 in adult T-ALL patients of 4.6% (7/152 cases) (4).…”

“…In addition, compared with SET-NUP214-negative patients, SET-NUP214-positive patients demonstrated a significantly increased rate of corticosteroid and chemotherapy resistance; however, this was not observed to negatively influence clinical outcome following allogeneic transplantation (12). However, there is not sufficient information on the clinical characteristics and treatment outcomes of patients carrying the SET-NUP214 fusion gene (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Furthermore, to the best of our knowledge, no case of B-cell ALL (B-ALL) carrying the SET-NUP214 fusion gene has been reported thus far.…”