Acute myeloid leukemia with t(7;21)(p22;q22) and 5q deletion: a case report and literature review

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.

Pediatric acute myeloid leukemia with t(7;21)(p22;q22)

“…The t(7;21)(p22;q22) resulting in a RUNX1‐USP42 fusion is an infrequent abnormality found in a subcategory of myeloid malignancies. To date, 12 cases with t(7;21)(p22;q22), including 11 AML patients and one MDS (refractory anemia with excess blasts—RAEB) patient, have been reported (summarized in Table ) . Counting the present three cases, there are a total of 14 AML patients with t(7;21).…”

“…Fourteen patients were reported to have anemia (Table ). Ji et al suggested the presence of anemia in patients with t(7;21) may be due to the 5q deletion causing haploinsufficiency of the RPS14 gene at 5q33.1. Happloinsufficiency of RPS14 has been associated with erythroid differentiation and this gene was proposed as a critical gene in MDS with isolated del(5q) .…”

“…A limited number of acute myeloid leukemia (AML) patients with the t(7;21)(p22;q22) have been reported in literature. Interestingly, the majority of these patients had additional chromosomal abnormalities, more frequently including deletions of the long arm of chromosome 5 (5q) or a rearrangement resulting in loss of a significant portion of 5q . Coexistence of t(7;21) and loss of 5q segment has been proposed to be a nonrandom finding in AML patients …”

Detection of rare reciprocal RUNX1 rearrangements by next‐generation sequencing in acute myeloid leukemia

“…B, Karyogram of 48,XY,+Y,der(7)t(3;7)(q?13;q?31),+8,t(16;21)(q24;q22)[18]/46,XY[2] by G-banding analysis. He had been diagnosed with standard-risk T-cell acute lymphocytic leukemia (T-ALL) 8.5 years earlier (95% blasts, CD2+, CD3+, CD4+, CD5+, CD8+, CD5+, CD7+, TdT++, Figure S1A).…”

The first case of acute myeloid leukemia with solitary t(6;7)(p21.3;p22) passenger translocation that developed at relapse after allogeneic hematopoietic stem cell transplantation in a patient with a normal karyotype at the initial diagnosis

“…AML is associated with 5q abnormalities and hyperploidy [1234567]. In terms of t(6;7), this abnormality was reported in three AML cases as a mainline abnormality included in complex chromosomal abnormality [8910].…”