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.     

t(8;21) prior to acute leukemia

A t(8;21)(q22;q22) without blood and bone marrow invasion by immature myeloid precursor cells occurred in a patient previously treated for polycythemia vera. The presence of a molecular rearrangement confirmed that the chromosomal abnormality was identical to that observed in acute leukemia with t(8;21). This case shows that the translocation, t(8;21), may occur in myelodysplasia and suggests that it can precede the appearance of overt leukemia.     

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.     

Immunophenotypic profile predictive of KIT activating mutations in AML1-ETO leukemia

Translocation (8; 21)/AML1-ETO is considered a favorable cytogenetic abnormality in acute myeloid leukemia (AML). However, associated KIT activating mutations confer poor outcome. The immunophenotype associated with KIT mutations in AML1-ETO has not previously been elucidated. We retrospectively reviewed the immunophenotype by flow cytometry of 56 cases of AML with t(8; 21) and compared them with 100 cases of AML without t(8; 21). In 21 t(8; 21) cases, we sought KIT mutations by direct sequencing. Although CD19 and CD56 were aberrantly expressed in 42 (75%) of 56 and 46 (82%) of 56 cases, respectively, with t(8; 21), these markers were only expressed in 4% and 25%, respectively, without t(8; 21) (P < .001). However, the 5 KIT-mutated cases (D816H, 3; D816Y, 1; and N822K, 1) of t(8; 21) AML had diminished CD19 expression (P = .04) with definite CD56 expression (P = .30) on myeloid blasts. Our study suggests that KIT activating mutations in AML with t(8; 21) are associated with diminished CD 19 and positive CD56 expression on leukemic blasts and, thus, can be phenotypically distinguished from AML1-ETO leukemias without KIT mutations.     

Molecular assignment of a translocation breakpoint in acute myeloid leukemia with t(8;21)

An 8;21 translocation is a common chromosome abnormality associated with acute myeloblastic leukemia with maturation (M2 of French-American-British (FAB) classification). We have isolated chromosome 21 Notl linking clones; pulsed field gel electrophoresis analysis with one clone (LL263) detected an altered fragment of Notl-digested leukemic cell DNA carrying t(8;21). The altered fragment was shown to be produced by the 8;21 translocation. The breakpoint in chromosome 21 was located about 13 kb to 100 kb proximal to the LL263 Notl site. Because the LL263 clone has a CpG island and is a short distance from the breakpoint, the clone itself may be considered as a candidate for part of the t(8;21) associated gene.     

A case of basophilic leukemia bearing simultaneous translocations t(8;21) and t(9;22)

We report a case of basophilic leukemia with simultaneous translocations of t(8;21) and t(9;22). The patient's clinical and hematologic findings were characteristic only of t(9;22) but not of t(8;21). This unusual cytogenetic phenomenon raises a challenge to the current concepts of primary chromosomal abnormalities in cancer.     

Simultaneous PML/RARalpha and AML1/ETO expression with t(15;17) at onset and relapse with only t(8;21) in an acute promyelocytic leukemia patient

We report a patient with acute promyelocytic leukemia with the common translocation (15;17) and PML-RARAalpha fusion gene. In relapse, blasts showed typical FAB M2 morphologic features, and the karyotype was 45,X, -Y,t(8;21). A reexamination of the leukemic cells at diagnosis revealed that an AML1-ETO fusion gene was also present at that time without cytogenetic evidence of t(8;21). In relapse, only t(8;21) was detected. Two different clones were identified by cytogenetic standard techniques. The association of two common translocations supervening in the same time in the same cells could not be established.     

Identification of ins(8;21) with AML1/ETO fusion in acute myelogenous leukemia M2 by molecular cytogenetics

A high percentage of cases of acute myelogenous leukemia (AML) of the M2 subtype show a rearrangement between the AML1 and ETO genes. The detection of the AML1/ETO fusion has clinical relevance because patients with this subtype have a good prognosis. We present the results of conventional and molecular cytogenetic studies in a patient with acute myelogenous leukemia French-American-British M2 classification, who had a complex karyotype involving chromosomes 8 and 21. Dual-color fluorescence in situ hybridization (FISH) using the AML1/ETO probe demonstrated a recombination of both genes on an add(8) chromosome. The use of other FISH probes (CEP8, c-myc and TEL21) and spectral karyotyping indicated that AML1/ETO fusion occurred as a consequence of a previously undescribed ins(8;21)(q22;q22.1q22.3).     

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)].     

Further characterization of acute myelogenous leukemia with t(8; 21) chromosome translocation

All seven patients with t(8; 21)(q22; q22) and one with a del(8)(q22) had a diagnosis of acute myelogenous leukemia (AML)-M2 type. Similar morphologies of leukemic cells with a t(8q?; 21q+) or with an 8q?, as well as the association of the latter with loss of a sex chromosome, indicated that the translocation or deletion of chromosome No. 8 at q22 may be essential to the phenotypic expression and loss of a sex chromosome in cells with the translocation. Seven patients (one in group I, four in group II, and two in group III) were in remission and four relapsed. All patients at relapse had acquired additional autosomal abnormalities, which were related to changes in cell morphology and relapse.