Acute myeloid leukemia (AML) with t(8;21)(q22;q22) relapsing as AML with t(3;21)(q26;q22)

We here report on an 48-year-old male patient with a primary diagnosis of acute myeloid leukemia (AML)-M2 with t(8;21)(q22;q22), who developed complete hematologic and molecular remission after induction chemotherapy. Thirteen months later, he relapsed and showed an AML-M2 with t(3;21)(q26;q22). Retrospectively, polymerase chain reaction (PCR) for AML1-EVI1 and EVI1 overexpression was performed on bone marrow and peripheral blood samples taken at diagnosis and during the first year after the first manifestation of AML to quantify the AML1-EVI1-positive clone. In a bone marrow sample taken 25 days from diagnosis, PCR for AML1-EVI1 was negative, and EVI1 expression, as assessed by quantitative real-time PCR, was within the same range as that of healthy controls. These data suggest that this patient developed a secondary therapy-related AML rather than a relapse.     

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

The t(7;21)(p22;q22) resulting in RUNX1‐USP42 fusion, is a rare but recurrent cytogenetic abnormality associated with acute myeloid leukemia (AML) and myelodysplastic syndromes. The prognostic significance of this translocation has not been well established due to the limited number of patients. Herein, we report three pediatric AML patients with t(7;21)(p22;q22). All three patients presented with pancytopenia or leukopenia at diagnosis, accompanied by abnormal immunophenotypic expression of CD7 and CD56 on leukemic blasts. One patient had t(7;21)(p22;q22) as the sole abnormality, whereas the other two patients had additional numerical and structural aberrations including loss of 5q material. Fluorescence in situ hybridization analysis on interphase cells or sequential examination of metaphases showed the RUNX1 rearrangement and confirmed translocation 7;21. Genomic SNP microarray analysis, performed on DNA extracted from the bone marrow from the patient with isolated t(7;21)(p22;q22), showed a 32.2 Mb copy neutral loss of heterozygosity (cnLOH) within the short arm of chromosome 11. After 2‐4 cycles of chemotherapy, all three patients underwent allogeneic hematopoietic stem cell transplantation (HSCT). One patient died due to complications related to viral reactivation and graft‐versus‐host disease. The other two patients achieved complete remission after HSCT. Our data displayed the accompanying cytogenetic abnormalities including del(5q) and cnLOH of 11p, the frequent pathological features shared with other reported cases, and clinical outcome in pediatric AML patients with t(7;21)(p22;q22). The heterogeneity in AML harboring similar cytogenetic alterations may be attributed to additional uncovered genetic lesions.     

t(8;21)(q22;q22) in blast phase of chronic myelogenous leukemia

The blast phase of chronic myelogenous leukemia (CML) frequently is associated with cytogenetic evidence of clonal evolution, defined as chromosomal aberrations in addition to the t(9;22)(q34;q11.2). We identified the t(8;21)(q22;q22) and other cytogenetic abnormalities by conventional cytogenetics and fluorescence in situ hybridization in 2 patients with t(9;22)-positive CML at the time of blast phase. The t(8;21), which typically is associated with a distinct subtype of de novo acute myeloid leukemia (AML) carrying the aml1/eto fusion gene, was accompanied by increased bone marrow myeloblasts (33%) in case 1 and extramedullary myeloid sarcoma in case 2, suggesting its possible role in disease progression. In case 1, the leukemic cells in aspirate smears had salmon-colored cytoplasmic granules, and immunophenotypic studies showed that the blasts expressed CD19. These findings suggest that the pathologic features of blast phase CML with the t(8;21) resemble those of de novo AML with the t(8;21).     

Two cases of acute myeloblastic leukemia (M2 type) with karyotypes 45X,-X,t(6;8)(q27;q22),inv(9) and 46,XY,t(8;21)(q22;q22),del(9)(q22)

Two patients with acute myelogenous leukemia (AML) are described. The first case is that of a patient with AML who had a low leukocyte alkaline phosphatase level associated with a variant (6;8)(q27;q22) translocation, coupled with loss of an X chromosome in bone marrow and unstimulated blood cells. The second case is that of an AML patient in whom the karyotype of the leukemic cells at the time of diagnosis was 46,XY,t(8;21)(q22;q22),del(9)(q22); at relapse, the patient acquired an additional chromosome #19. The lack of involvement of chromosome #21 in the first case, as well as the occurrence of an abnormality of chromosome #9, in addition to the t(8q-;21q+) in the second case are discussed with reference to the character of the possible specific chromosomal events in patients with type M2 AML.     

Ph-positive chronic myeloid leukemia with t(8;21)(q22;q22) in blastic crisis.

A patient diagnosed with chronic myeloid leukemia was studied periodically during his illness. The result showed the presence of a Philadelphia (Ph) chromosome by a 9;22 translocation as a single abnormality to the time of blastic crisis. At that time, the chromosome studies showed a clonal evolution. Furthermore, a second derivated line was added to the Ph line. This new anomaly consisted of a 8;21 translocation, considered as specific of M2 type acute nonlymphoblastic leukemia of French-American-British classification.     

Duplication 15q in a patient with t(8;21) acute myeloblastic leukemia (M2)

We present unique chromosomal abnormalities found in a patient with acute myeloblastic leukemia (AML) of French-American-British subtype M2. The patient was referred for an evaluation of chromosomal anomaly associated with AML. She was found to have an abnormal karyotype 46,XX,t(8;21)(q22;q22), and a questionable dup(15)(q15q22) in the majority of cells analyzed. Two cells had the same chromosomal anomalies plus a duplicated derivative chromosome 21 [der(21)t(8;21)(q22;q22)]. These cytogenetic findings were confirmed by fluorescence in situ hybridization utilizing the appropriate DNA probes. To our knowledge, this is the first case report of a combination of the translocation between chromosomes 8 and 21, a duplication of chromosome 15 [dup(15)(q15q22), and a duplicated derivative chromosome 21 [der(21)t(8;21)(q22;q22)].     

Molecular characterization of AML with ins(21;8)(q22;q22q22) reveals similarity to t(8;21) AML

In acute myeloid leukemia (AML), nonrandom clonal chromosome aberrations are detectable in ～ 55% of adult cases. Translocation t(8;21)(q22;q22) resulting in the 5'RUNX1/3'RUNX1T1 fusion gene occurs in ～ 8% of AML cases. Also, ins(8;21) and ins(21;8) have been described that show a broad heterogeneity at the molecular level with inserted fragment sizes ranging from 2.4 to 44 Mb. Microarray-based comparative genomic hybridization (arrayCGH) in 49 intermediate-risk AML and RT-PCR-based screening in 532 AML cases allowed the detection of ins(21;8)/ins(8;21) in three cases; arrayCGH and subsequent RT-PCR revealed an ～ 0.5 Mb sized inserted fragment generating the 5'RUNX1/3'RUNX1T1 fusion gene in one case with a submicroscopic ins(21;8)(q22;q22q22) whereas the other two cases were identified by banding analysis and RT-PCR, respectively. Gene expression profiling (GEP) and a detailed review of the literature highlighted similar biological features of AML cases with ins(21;8)/ins(8;21) and t(8;21)(q22;q22). Our study demonstrates the potential of high-resolution array-based analysis and GEP and provides further evidence that AML with insertions generating the 5'RUNX1/3'RUNX1T1 fusion not only biologically resemble the t(8;21)(q22;q22) AML subgroup, but might also share its prognostically favorable clinical behavior. Thus, similar treatment options should be considered in these patients.     

An unusual three-way translocation t(21;8;1)(q22;q22;q32) in a case of acute myeloid leukemia (M2)

Variant forms of the classic translocation t(8;21) are uncommon and account approximately 3% of all t(8;21)(q22;q22) in acute myeloid leukemia (AML) patients. These forms involve chromosomes 8, 21, and other chromosomes. Here we report a Tunisian patient with a complex rearrangement t(21;8;1)(q22;q22;q32) revealed by conventional chromosomal study at diagnosis. Fluorescence in situ hybridization study revealed the presence of the AML1-ETO chimeric gene on the derivative chromosome 8. To the best of our knowledge, this is the second case of t(21;8;1) of AML-M2 reported in the literature with the involvement of the same breakpoint at 1q32. This illustrates that this complex translocation is rarely encountered in AML and reinforces the fact that this region may harbour a critical gene candidate that may play an important role in the pathogenesis of AML. More cases are needed to elucidate its clinical features and prognosis.     

A t(11;21)(q13;q22) in Ph-positive chronic myelogenous leukemia

Reciprocal translocations, in addition to that of the Ph chromosome, though rare, have been reported in chronic myelogenous leukemia (CML). We describe here a case of Ph-positive CML with a new translocation, t(11;21)(q13;q22), and missing Y, which were present both during transformation to the blastic crisis and in the subsequent reversion to the chronic phase. The possible significance of this abnormality is discussed.