Abstract
The gene RUNX1 at chromosome 21q22 encodes the alpha subunit of Core binding factor (CBF), a heterodimeric transcription factor involved in the development of normal hematopoiesis. Translocations of RUNX1 are seen in several types of leukemia with at least 21 identified partner genes. The cryptic t(7;21)(p22;q22) rearrangement involving the USP42 gene appears to be a specific and recurrent cytogenetic abnormality. Eight of the 9 cases identified in the literature with this translocation were associated with acute myeloid leukemia (AML), with the remaining case showing refractory anemia with excess blasts, type 2. Herein, we present a patient with two preceding years of leukopenia and one year of anemia prior to the diagnosis of AML, NOS with monocytic differentiation (myelomonocytic leukemia) whose conventional cytogenetics showed an abnormal clone with 5q deletion. Interphase FISH using LSI RUNX1/RUNXT1 showed three signals for RUNX1. FISH studies on previously G-banded metaphases showed the extra RUNX1 signal on the short arm of chromosome 7. Further characterization using the subtelomeric 7p probe showed a cryptic 7;21 translocation. Our case and eight previously reported leukemic cases with the t(7;21)(p22;q22) appear to share similar features including monocytic differentiation, immunophenotypic aberrancies (often with CD56 and/or CD7), and a generally poor response to standard induction chemotherapy. About 80% of these cases had loss of 5q material as an additional abnormality at initial diagnosis or relapse. These findings suggest that t(7;21) may represent a distinct recurrent cytogenetic abnormality associated with AML. The association between the t(7;21) and 5q aberrancies appears to be non-random, however the pathogenetic connection remains unclear. Additional studies to evaluate for RUNX1 partner genes may be considered for AML patients with RUNX1 rearrangement and 5q abnormalities; however knowledge of the prognostic implications of this rearrangement is still limited.
Highlights
Gene fusion and chromosomal abnormalities play vital roles in tumorigenesis, including hematologic malignancies [1]
Many of these fusion genes involve the translocation of Runt-related transcription factor 1 (RUNX1), known as acute myeloid leukemia 1 protein (AML1) [3]
The gene RUNX1 at chromosome 21q22 encodes the alpha subunit of core binding factor (CBF), a heterodimeric transcription factor involved in the development of normal hematopoiesis
Summary
Gene fusion and chromosomal abnormalities play vital roles in tumorigenesis, including hematologic malignancies [1]. More than 100 fusion genes have been reported in acute myeloid leukemia (AML) [2]. Many of these fusion genes involve the translocation of Runt-related transcription factor 1 (RUNX1), known as acute myeloid leukemia 1 protein (AML1) [3]. The gene RUNX1 at chromosome 21q22 encodes the alpha subunit of core binding factor (CBF), a heterodimeric transcription factor involved in the development of normal hematopoiesis. The deletion of all or part of long arm of chromosome 5 (del(5q)) is a recurrent abnormality in AML and MDS patients. While the association between del(5q) and AML are still unclear, a deletion of 1.5 Mb region at 5q31.1 flanked by genes IL-9 and EGR-1 has been reported to be related with AML [6]. Del(5q) is mostly part of the complex karyotype in many AML cases, which makes it more difficult to reveal its significance
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