47，XX，del（12）（q24），＋t（12；21）（q24；q22）一例

患者女，21岁．2003年3月29日来我科婚前咨询。查体：身高140cm．体重46kg。系第2胎足月顺产．外观先天愚型貌，生活能自理，有正常月经来潮。其父母非近亲婚配，表型正常，孕2产2，其母孕期正常。其姐25岁。表型正常．已婚并生育一子，表型亦正常，否认有家族遗传病史。     

Acute myelomonocytic leukemia with bone marrow eosinophilia and inv(16)(p13q22),t(1;16)(q32;q22)

A two-year-old girl presenting with de novo acute myelomonocytic leukemia with eosinophilia (French-American-British [FAB] classification, M4Eo) and inv(16)(p13q22), t(1;16)(q32;q22) involving the same chromosome 16 is described. This is the second report of a variant translocation of an inverted chromosome 16 with chromosome 1 at 1q32. However, the segment 1q32----1qter has been exchanged for 16q22----qter and not 16p13----pter, as reported in the previous case. The additional break at 1q32 and the juxtaposition of 1q32----qter onto chromosome 16 could be relevant to the pathogenesis of the disease.     

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.     

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.     

Molecular cytogenetic investigations in a novel complex variant of t(8;21)(q22;q22) with ins(15;21)(q15;q22.2q22.3) in a patient with AML-M2 subtype

Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease characterized by the aberrant proliferation of myeloid stem cells, reduced apoptosis and blockage in cellular differentiation. The present report describes the results of hematological, cytogenetic, and fluorescence in situ hybridization (FISH) analysis in a 25-year-old man diagnosed with AML-M2. Cytogenetic as well as FISH analysis revealed a complex translocation involving four chromosomes, with the karyotype 45,−Y,der(X)t(X;8)(p21;q22),der(8)t(8;21)(q22;q22),ins(15;21)(q15;q22.2q22.3),der(21)t(8;21)(q22;q22). The breakpoints at 8q22 and 21q22 suggested a rearrangement of the RUNX1T1 (alias ETO) and RUNX1 (previously AML1) genes, respectively. Using a dual-color FISH test with RUNX1T1 and RUNX1 probes, we demonstrated an RUNX1/RUNX1T1 fusion signal on the derivative chromosome 8, establishing this translocation as a novel complex variant of t(8;21)(q22;q22).     

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.     

A possible specific chromosome marker for monocytic leukemia: three more patients with t(9;11)(p22;q24) and another with t(11;17)(q24;q21), each with acute monoblastic leukemia

An apparently balanced 9;11 reciprocal translocation with break points most likely at 9p22 and 11q24 was found in 3 patients with acute monocytic leukemia [M5 in the French-American-British (FAB) classification schema]. This translocation was not observed in 6 other patients with M5 acute nonlymphocytic leukemia (ANLL) or in chromosome studies on 143 patients with other types of ANLL. This study supports the previously published suggestion that such 9;11 translocations may be associated with some patients with M5 ANLL. In this report, we have also included a patient with M5 ANLL who had an 11;17 translocation with break points apparently at 11q24 and 17q21. Perhaps this is a variant translocation of chromosome No. 11, which may also be associated with monocytic leukemia.     

Re-evaluation of GM2346 from a del(16)(q22) to t(4;16)(q35;q22.1)

Reassessment of the cytogenetics of a patient previously karyotyped as del(16)(q22) demonstrates the presence of a balanced translocation, t(4;16)(q35;q22.1). This patient should not be included in any future comparison involving the clinical features of patients with deletions of the long arm of chromosome 16.     

A new variant t(6;15;17)(q25;q22;q21) in acute promyelocytic leukemia: fluorescence in situ hybridization confirmation

Acute promyelocytic leukemia (APL) is characterized by the t(15;17)(q22;q21), which results in the fusion of the promyelocytic leukemia (PML) gene at 15q22 with the retinoic acid alpha-receptor (RARalpha) at 17q21. The 2 chimeric genes PML/RARalpha and RARalpha/PML are thought to play a role in leukemogenesis. We report a case of APL in a patient carrying an apparently complex variant translocation identified as t(6;15;17) by R-banding and whole chromosome 15 and 17 painting. However, FISH analysis with a PML/RARalpha dual-color kit showed a more complex translocation, resulting presumably from a two-step rearrangement, with PML-RARalpha fusion gene located as expected on the der(15) but the residual 5'-RARalpha signal located on the der(6). The patient achieved complete remission with all-trans retinoic acid treatment associated with chemotherapy. This case illustrates the usefulness of combined cytogenetics, FISH, and molecular biology to evidence the PML/RARalpha fusion gene in complex cases.     

46，XX，t（1；7）（q21；q22）pat一例

患者女,28岁,婚后于2000年9月孕1月余“不全流产”,2003年2月,2004年12月“稽留流产”,3次均无明显诱因,而且每次都需要治疗才能怀孕,于2006年4月生育一女孩,现11个月,无明显异常,未做染色体检查,孕期拒绝做产前诊断。夫妻表型、智力正常,身体健康,非近亲结婚。患者母亲第1、2孕均于孕3个月流产,后生育3个女儿,表型正常,该患者为第3个女儿,患者二姐生育一男孩,表型、智力正常。细胞遗传学检查:取夫妇静脉血肝素抗凝,经常规培养制片,G显带处理,分析30个中期分裂相。患者核型为46,XX,t(1;7)(1pter→lq21∷7q22→7qter;7pter→7q22∷lq21→1q…     

Novel t(8;17)(q23;q24.2) and t(9;22)(p24.1;q12.2) in acute megakaryoblastic leukemia AML-M7 subtype in an adult patient

The strong association of diagnostic karyotype with clinical outcome has made cytogenetics one of the most valuable diagnostic and prognostic tools for acute myeloid leukemia (AML). The subtype M7 is a rare disease of the megakaryoblastic lineage and is mostly associated with complex abnormal karyotype. We describe the clinical, morphologic, immunophenotypic, and cytogenetic findings in the case of a 39-year-old man with acute megakaryoblastic leukemia (AML-M7). Cytogenetic analysis revealed two translocations, t(8;17)(q23;q24.2) and t(9;22)(p24.1;q12.2), at presentation; to our knowledge, this combination is a novel finding for acute megakaryoblastic leukemia. The patient responded to induction therapy, achieving complete remission after 9 days of therapy.     

t(6;12)(q23;q13) and t(10;16)(q22;p11) in a phyllodes tumor of breast.

Cytogenetic analysis of short-term cultures from a phyllodes tumor showed clonal chromosome changes including t(6;12)(q23;q13) and t(10;16)(q22;p11). This is the first reported karyotype in this tumor type. We discuss the breakpoints of these translocations in relation to the involvement of possible candidate genes.