T(1;21;8)(p34;q22;q22): a novel variant of t(8;21) in acute myeloblastic leukemia with maturation

The complex variants of t(8;21) involving chromosomes 8 and 21 as well as another chromosome account for approximately 3% of acute myeloid leukemia patients. We report here a 30-year-old male patient with AML-M2. Fluorescence in situ hybridization analysis using dual-color fluorescence ETO and AML1 probes located at 8q22 and 21q22 respectively showed an AML1/ETO fusion signal on the derivative chromosome 8. Whole chromosome painting probes were used for chromosome 1, 8 and 21 and revealed a three-way translocation (1;21;8)(p34 ~ p35;q22;q22). Involvement of chromosome region 1p34 has never been reported earlier, although region 1p35 as a variant in AML with t(8;21) has been reported with an AML1/ETO fusion signal on the 1p35 rather than der(8). In conclusion, combining conventional karyotype, FISH or RT-PCR analyses are a rational strategy for the identification of the complex variants of t(8;21) translocation which could be critical events responsible for leukemogenesis.     

The t(10;11)(p14;q21) translocation in three children with acute myeloblastic leukemia

A total of 161 cases of pediatric de novo acute myeloblastic leukemia (AML) have been reviewed, for which complete karyotyping was available and three cases (2%) were identified with t(10;11)(p14;q21). Two of the three children were infants with monoblastic (FAB M5) leukemia and the third was an adolescent with undifferentiated myeloid (FAB M1) leukemia. Both infants presented with increased levels of lactate dehydrogenase. None of these cases had increased eosinophils. One of the infants is in remission 18+ months after diagnosis and intensive chemotherapy; the two other children attained brief initial remissions but succumbed to their disease within 11 months of diagnosis. The prognosis of such children appears to be similar to that of cases of AML lacking this translocation.     

伴t(8;21)(q22;q22)易位的急性双表型白血病的临床研究

Objective： To report 4 cases of biphenotypic acute leukemia （BAL） with t（8;21）（q22;q22）, and analyze the characteristics of morphology, immune phenotype, chromosome karyotype （MIC） and clinical manifestations. Methods： The BAL patients with t（8;21）（q22;q22） （group A） were compared with the randomly selected BAL patients with other clonical chromosomal changes （group B） and acute myeloid leukemia M2 cases with t（8;21）（q22;q22） （group C） in MIC and clinical features. Results： BAL with t（8;21）（q22;q22） showed acute myeloid leukemia with high percentages of blast cells morphologically; revealed co-positive to B-lymphoid and myeloid lineages, frequent and high expressions of CD34 and CD33; were responsive to chemotherapy for myeloid and lymphocytic leukemia simultaneously well. Conclusion： A new subset of BAL with t（8;21）（q22;q22） was reported, and this suggests that the leukemia colony with t（8;21）（q22;q22） might originate from early phase of hematopoiesis.     

伴t(8;21)(q22;q22)易位的急性双表型白血病的临床研究

目的:报道新发现4例伴t(8;21)(q22;q22)易位的急性双表型白血病(biphenotypic acute leukemia,BAL),分析其细胞形态学、免疫表型、染色体核型分型及临床特征。方法:将4例伴t(8;21)(q22;q22)易位的BAL(A组),与随机挑选同期发现的伴其他克隆性染色体改变的BAL(B组)和伴t(8;21)(q22;q22)的M2b(C组)病例对照,对染色体核型分型及临床特点比较分析。结果:伴t(8;21)(q22;q22)易位的BAL特点如下:①无显著男女性别差异;②发病年龄较轻;③外周血白细胞计数不增高;④骨髓细胞形态学显示为粒细胞白血病,且原始细胞显著增多;⑤免疫表型均为B淋巴系和髓系共表达的BAL,CD34表达阳性,且为高表达;⑥染色体改变除t(8;21)(q22;q22)易位外,亦常见性染色体缺失,与(acute myeloid leukemia,AML)AML-M2b的特点相符;亦出现复杂染色体改变,符合BAL的特点。⑦对兼顾髓系和淋巴系的联合治疗方案反应较好,与B组的BAL类似,1例单用AML方案(MA)治疗者NR,后死亡。结论:报道新发现的一组伴t(8;21)(q22;q22)易位的BAL,提示此类患者的白血病细胞克隆起源可能较早。     

Variant translocation t(3;15)(q21;q22) in a patient with acute promyelocytic leukemia

Bone marrow cells from most patients with acute promyelocytic leukemia contain a highly specific cytogenetic rearrangement, a reciprocal translocation between the long arms of chromosomes 15 and 17. Several cases of variant translocations involving 17q but not 15q have been reported, leading to the suggestion that the break in 17q rather than the one in 15q is the crucial change in the regular t(15;17). We describe a hematologically typical case of acute promyelocytic leukemia with a t(3;15)(q21;q22). This is the first report in this leukemia subset of a variant translocation affecting 15q without involvement of 17q.     

Translocation t(9;11)(p21;q23) in pediatric de novo and secondary acute myeloblastic leukemia.

The t(9;11)(p21;q23) has been associated with characteristic clinical features and a superior treatment outcome in previously untreated pediatric acute myeloblastic leukemia (AML), but has not been well studied in children with secondary AML. This translocation was detected in 6.7% of de novo and 46% of secondary AML patients treated at St Jude Children's Research Hospital over an 11-year period. Clinical, immunophenotypic, and morphologic characteristics were examined for the cases of t(9;11) secondary AML (n = 12) and compared with findings for children with t(9;11) de novo AML (n = 12). Patients with t(9;11) secondary AML were older at diagnosis, had higher hemoglobin levels, and central nervous system leukemia or hepatosplenomegaly was less frequent. These differences probably reflect survival of the first malignancy and close clinical scrutiny during post-treatment follow-up. Whereas the t(9;11)(p21;q23) occurred exclusively in the French-American-British (FAB) M5 subtype in de novo AML, the FAB M0 and M4 subtypes were also represented in secondary cases. The complete remission rate was somewhat higher for the de novo AML group (91 vs 58%; p = 0.16); their event-free survival was clearly superior to that for children with t(9;11) secondary AML (p = 0.003). Host differences related to the previous malignancy or its treatment could explain the poorer clinical outcome for patients with t(9;11) secondary AML. Alternatively, there could be critical differences at the translocation site or additional, hidden molecular events, that explain the different outcomes.     

Three way translocation in a new variant of t(8;21) acute myeloid leukemia involving Xp22

The t(8;21)(q22;q22) is one of the most frequent chromosomal abnormality associated with acute myeloid leukemia (AML) M2 sub type. The additional chromosomal abnormalities including structural and numerical are frequently reported with the translocation, t (8;21)(q22;q22). We report a case of AML-M2 with t(X;8;21)(p22;q22;q22) associated with loss of Y chromosome. Using a dual color fluorescence in situ hybridization (FISH) analysis with ETO and AML1 probes, we demonstrated an ETO/AML1 fusion signal on the derivative chromosome 8 and one ETO signal on derivative Chromosome Xp22. The patient did not respond to therapy and follow-up of cytogenetics revealed same chromosome abnormality. Hence, this three way translocation involving X chromosome might be associated with poor prognosis.     

A novel t(8;13)(q21;q22) translocation in a pediatric lipoma

Pediatric lipomas are rare and their etiology is unknown. As in adult lipomas, a segment of 12q13-q15 has been documented as a common chromosomal rearrangement region. Here, we report a pediatric lipoma case without rearrangement of 12q13-q15 but with an apparently balanced translocation involving chromosomes 8 and 13 [t(8;13)(q21;q22)] detected by routine cytogenetic analysis, and small deletions on 5q21.1 and 8q21.11 detected by array comparative genetic hybridization. The small deletion on 8q21.11 is possibly due to chromosomal instability at the breakpoint of the translocation.     

Mutations in the receptor tyrosine kinase pathway are associated with clinical outcome in patients with acute myeloblastic leukemia harboring t(8;21)(q22;q22).

AML1-MTG8 generated by t(8;21) contributes to leukemic transformation, but additional events are required for full leukemogenesis. We examined whether mutations in the receptor tyrosine kinase (RTK) pathway could be the genetic events that cause acute myeloblastic leukemia (AML) harboring t(8;21). Mutations in the second tyrosine kinase domain, juxtamembrane (JM) domain and exon 8 of the C-KIT gene were observed in 10, one and three of 37 AML patients with t(8;21), respectively. Three patients showed an internal tandem duplication in the JM domain of the FLT3 gene. One patient had a mutation in the K-Ras gene at codon 12. As the occurrence of these mutations was mutually exclusive, a total of 18 (49%) patients showed mutations in the RTK pathway. These results suggest that activating mutations in the RTK pathway play a role in part as an additional event leading to the development of t(8;21) AML. The 6-year cumulative incidence of relapse in patients with RTK pathway mutations was 79.8%, compared with 13.5% in patients lacking such mutations (P=0.0029). Furthermore, the 6-year relapse-free survival in patients with mutations was 18% compared to 60% in those without mutations (P=0.0340), indicating that RTK mutations are associated with the clinical outcome in t(8;21) AML.     

Expression of fragile site 8q22 in peripheral blood lymphocytes taken from patients with acute leukemia M2 having t(8;21)(q22;q22)

The relation between the expression of common fragile sites and chromosomal breakpoints in neoplastic cells in the same patients has not been well studied. In the present study, the frequency and distribution of aphidicolin-induced breaks on chromosomes 8 and 21 in peripheral blood lymphocytes (PBL) taken from three patients with acute myeloid leukemia, French-American-British classification type M2, having chromosomal translocation t(8;21)(q22;q22) (M2t) were studied prior to any initial treatment. Seven patients with other types of acute leukemia without t(8;21) and 13 healthy people were also studied. In PBL from patients with M2t, the numbers of chromosomal breaks were 1, 7 and 3/216 metaphasees at bands 8q21, 8q22 and 8q24, respectively; the frequencies at 8q22 and 8q24 being significantly higher than those for patients with the other leukemias and for the healthy subjects (p less than 0.001 and p less than 0.01, respectively). These results suggest that the fragility on chromosome 8q21-24 is related to a predisposition to this particular type of leukemia.     

A novel translocation t(3;22)(q21;q11) involving 3q21 in myelodysplastic syndrome-derived overt leukemia with thrombocytosis

We report here a novel translocation t(3;22)(q21;q11) in myelodysplastic syndrome (MDS)-derived overt leukemia with thrombocytosis. A 44-year-old female was initially diagnosed as MDS with a low platelet count and normal karyotype. After 4 months, blood leukemic cells and platelets rapidly increased concomitantly and a diagnosis of acute myeloblastic leukemia (AML M1) was made. Chromosome analysis showed 46, XX, t(3;22)(q21;q11) in 14 of 20 metaphases. Fluorescence in situ hybridization analysis confirmed both the der(3)t(3;22) and the der(22)t(3;22). Our results suggest that unidentified gene(s) at 3q21 breakpoint may be implicated in the pathogenesis of abnormal thrombopoiesis as observed in the 3q21q26 syndrome.     

A new specific chromosomal rearrangement, t(11;20)(p15;q11), in myeloblastic leukemia with maturation

The translocation t(11;20)(p15;q11) was found as the sole acquired clonal chromosome abnormality in two patients with acute myeloid leukemia. The bone marrow morphology in both cases corresponded to the M2 subtype of the French-American-British (FAB) classification. None of the patients achieved complete remission, and both died less than 6 months after diagnosis. This particular translocation has not previously been reported in acute nonlymphocytic leukemia.