A case of atypical myelodysplastic syndrome with micromegakaryocytes,normal platelet count,and t(3;12)(q21;p13) with inv(3)(q21q26)

A 49-year-old woman patient with atypical myelodysplastic syndrome (MDS) showing a der(3)t(3;12)(q21;p13), and der(12)t(3;12)(q21;p13)inv(3)(q21q26) as an acquired chromosomal abnormality in the bone marrow is described. The chromosomal breakpoints of the presented complex aberration with combination of the inv(3)(q21q26) and t(3;12)(q21;p13) were defined by fluorescence in situ hybridization (FISH) with yeast artificial chromosomes (YACs). The inv(3) is a relatively frequent chromosomal rearrangement in patients with myeloid malignancies and dysmegakaryopoiesis and t(3;12)(q26;p13) has also been reported as a recurrent abnormality in MDS and in blast crisis of chronic myelogenous leukemia (CML). Whereas the t(3;12), inv(3), and t(3;3) are associated with a very poor prognosis, our patient surprisingly had a mild clinical course. Genes Chromosomes Cancer 20:292–298, 1997. © 1997 Wiley-Liss, Inc.     

Translocation t(11;14)(q13;q32) in chronic lymphoid disorders.

The translocation t(11;14)(q13;q32) has been described in a spectrum of B-lymphoproliferative diseases and involves a putative oncogene, BCL1, which maps to chromosome band 11q13. Recent evidence indicates that this abnormality may delineate particular subtypes of lymphoma, such as intermediate lymphocytic and centrocytic lymphomas. Thus the possible significance of the t(11;14) within B-cell disorders should be reexamined in the light of a more objective approach to classifying these diseases by morphology, histology, and immunophenotype. We describe 16 patients with t(11;14)(q13;q32) from a series of 90 patients with chronic lymphoid disorders in whom clonal chromosome abnormalities were detected. All the cases were leukemic: prolymphocytic (B-PLL; 4/15 cases), chronic lymphocytic leukemia (CLL) with increase in prolymphocytes (2/9 cases), or non-Hodgkin lymphoma in leukemic phase, intermediate (3/4 cases), lymphoplasmacytic (2/2 cases), splenic lymphoma with villous lymphocytes (4/18 cases), and follicular (1 case). None of the CLL (25) or hairy cell leukemia cases (15) had t(11;14). Our findings showed that t(11;14) occurred in leukemias of mature B cells with lymphoplasmacytic features as judged by morphology and immunophenotype.     

Unbalanced translocation der(11)t(11;12)(q23;q13): a new recurrent cytogenetic aberration in myelodysplastic syndrome with a complex karyotype

Cytogenetic abnormalities are observed in approximately one half of cases of myelodysplastic syndrome (MDS). Partial or complete chromosome losses and chromosome gains are frequently found, but there is a relatively high incidence of unbalanced translocations in MDS. We describe here two cases of MDS with an unbalanced translocation, der(11)t(11;12)(q23;q13). Both patients were 69 years of age and diagnosed with refractory anemia with excess of blasts in transformation (RAEB-t) according to the high percentage of blasts in the peripheral blood. Cytoplasmic hypogranulation of neutrophils was evident as a dysplastic change. The blasts were positive for CD4 and CD41a as well as CD13, CD33, CD34 and HLA-DR in both cases. Chromosome analysis showed complex karyotypes including a der(11)t(1;11)(q11;p15)t(11;12)(q23;q13) in case 1 and der(11)t(11;12)(q23;q13) in case 2 plus several marker chromosomes. Spectral karyotyping confirmed the der(11)t(11; 12)(q23;q13) and clarified the origin of marker chromosomes, resulting in del(5q) and del(7q). Fluorescence in situ hybridization (FISH) analyses with a probe for the MLL gene demonstrated that the breakpoints at 11q23 were telomeric to the MLL gene in both cases. FISH also showed that the breakpoint at 11p15 of the case 1 was telomeric to the NUP98 gene. Considering another reported case, our results indicate that the der(11)t(11;12)(q23;q13) is a recurrent cytogenetic abnormality and may be involved in the pathogenesis of advanced-stage MDS.     

Concurrent presence of inv(14)(q11q32) and t(4;11)(q21;q23) in Pre-B Acute Lymphoblastic leukemia

The inv(14)(q11q32) is a non-random chromosomal aberration which has been associated with a variety of T-cell malignancies. We have studied a case of inv(14)(q11q32) that is unique in several respects. First, the inversion, which is expressed at the mRNA level, occurred in the context of a pre-B acute lymphoblastic leukemia (ALL) as opposed to a T-cell malignancy. Second, cloning and sequencing of the inversion revealed that it resulted from a fusion between an immunoglobulin heavy chain variable (V) segment and a T-cell receptor delta diversity (D) segment. In addition, the patient had a second chromosomal abnormality at diagnosis, a t(4;11)(q21;q23) which disrupted the MLL gene. The fact that there were two distinct chromosomal abnormalities at diagnosis enabled us to address the question of leukemic clonal evolution during the course of this patient's disease. We present evidence suggesting that the t(4;11)(q21;q23) occurred first, with the inv(14)(q11q32) occurring as a second event.     

Correlation between losses of IGH or its segments and deletions of 13q14 in t(11;14) (q13;q32) multiple myeloma

Multiple myeloma (MM) is a malignancy of the plasma cells (PCs) characterized by a wide variety of genetic and chromosomal abnormalities. In recent years, major attention was drawn to the significance of chromosomal aberrations involving chromosome arm 13q and the IGH region on chromosome band 14q32 as a prognostic indicator in MM. In this study we applied a combined cell morphology and FISH method for the analysis of coexistence of t(11;14)(q13;q32) with deletions of the long arm of chromosome 13 (Δ13) in PCs from 51 MM patients using several probes for the 13q14, 11q13, and IGH regions. We found 15 different variants of the t(11;14) that are the consequence of different 11q13 breakpoints and various deletions of Variable (del IGH Var) or Constant (del IGH Const) IGH segments and also duplications and losses of the IGH gene on the normal nontranslocated chromosome 14 as well as IGH/Cyclin D1 (CCND1) fusion on der(14) and CCND1/IGH fusions on der(11). A strong association between Δ13 and specific variants of t(11;14) was found: variants with deletion of the IGH gene or its segments were found only in MM cases with deleted chromosome 13, while the common translocation t(11;14) was found only in the MM cases with normal chromosome arm 13q. In contrast, we did not find any association between Δ13 and deletions of the IGH gene or its segments in the MM patients with t(4;14)(p16;q32). © 2009 Wiley‐Liss, Inc.     

Der(16)t(1;16)(q21;q13) as a secondary structural aberration in yet a third sarcoma,extraskeletal myxoid chondrosarcoma

Cytogenetic analysis of an extraskeletal myxoid chondrosarcoma revealed a der(16)t(1;16)(q21;q13) in addition to the t(9;22)(q22;q12) described as characteristic for this chondrosarcoma clinicohistopathologic subtype. An identical der(16) has been identified as the most common secondary structural aberration in Ewing's sarcoma and alveolar rhabdomyosarcoma. Genes Chromosomes Cancer 20:425–427, 1997. © 1997 Wiley-Liss, Inc.     

Two new chromosomal abnormalities in chronic myelogenous leukemia 46,XY,t(9;15;22)(q34;q22;q11) and 46,XY,t(6;9;12;22)(p21;q34;q24;q11)

Two new variant cases of chronic myelogenous leukemia (CML) are presented. The first case is a 19-year-old male with a 46,XY,t(9;15;22)(q34;q22;q11) karyotype. The second case is a 75-year-old man with a 46,XY,t(6;9;12;22)(p21;q34;q24;q11) karyotype. In both cases, the prognosis was no different from those cases of CML with the standard t(9;22) as the only abnormality. We recommend that all unusual translocations be reported.     

Chronic lymphocytic leukemia with t(14;19)(q32;q13) is characterized by atypical morphologic and immunophenotypic features and distinctive genetic features

The t(14;19)(q32;q13) involving the IGH@ and BCL3 loci is an infrequent cytogenetic abnormality detected in B-cell malignancies. We describe the clinicopathologic, cytogenetic, and molecular genetic characteristics of 14 cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) with t(14;19)(q32;q13). All patients (10 men and 4 women) had lymphocytosis; 10 had lymphadenopathy. Blood and bone marrow lymphocytes were predominantly small, but cytologically and immunophenotypically atypical. In all cases, t(14;19) was found in the neoplastic stem line; it was the sole abnormality in 4. Ten cases showed additional cytogenetic abnormalities, including trisomy 12 in 9 and complex karyotypes in 7. Fluorescence in situ hybridization demonstrated IGH@/BCL3 fusion gene in all cases. In all cases, the IGHV genes were unmutated, but only 7 expressed ZAP70. Seven cases preferentially used IGHV4-39. Our results indicate that t(14;19)(q32;q13) identifies a subset of CLL/SLL with distinctive clinicopathologic and genetic features. Furthermore, t(14;19) may represent an early, possibly primary, genetic event.     

<Emphasis Type="Italic">RABGAP1L</Emphasis> gene rearrangement resulting from a der(Y)t(Y;1)(q12;q25) in acute myeloid leukemia arising in a child with Klinefelter syndrome

In this study, we report the molecular cytogenetic characterization of an acute myeloid leukemia with a der(Y)t(Y;1)(q12;q25) in bone marrow cells in a child with Klinefelter syndrome. Conventional cytogenetics demonstrated the unbalanced translocation, i.e., a trisomic 1q25-qter juxtaposed to Yq12 replaced the terminal segment of chromosome Y was acquired and present only on bone marrow cells. Fluorescence in situ hybridization showed that the breakpoint at 1q25 disrupted RABGAP1L, a strongly expressed gene in CFU-GEMM, erythroid cells, and megakaryocytes, while the Yq12 breakpoint fell within the heterochromatic region. As der(Y)t(Y;1)(q12;q25) was an isolated cytogenetic change, RABGAP1L rearrangement as well as gene(s) dosage effects correlated to 1q25-qter trisomy, and Yq12-qter loss may make a major contribution to leukemogenesis and/or disease progression. Maria Cristina Roberti and Roberta La Starza should be regarded as joint first authors.     

染色体46,XX,t(1;4)(q42;q35)平衡易位一例

目的报道染色体平衡易位家系1例。方法检查父母及女儿染色体,采用外周血淋巴细胞培养法,G显带。结果父亲染色体核型为46,XY。母亲染色体核型为46,XX,t(1;4)(q42;q35)。女儿染色体核型为46,XX,der(1)t(1;4)(q42;q35),der(4)t(1;4)(q42;q35)。结论母亲染色体发生t(1;4)(q42;q35)平衡易位并遗传给下一代。     

Chronic myeloid leukemia in blast phase associated with t(3;8)(q26;q24)

We previously reported a recurrent t(3;8)(q26;q24) translocation involving EVI1 in five patients with myelodysplastic syndrome or acute myeloid leukemia. Here we report the same structural abnormality in a case of chronic myeloid leukemia in blast phase. The t(3;8)(q26;q24) occurred several months after the initial diagnosis of chronic myeloid leukemia, while the patient was being treated with a tyrosine kinase inhibitor. We confirmed rearrangement of EVI1 by fluorescence in situ hybridization assay using a dual-color break-apart probe set that spans the EVI1 region. Our findings demonstrate that, similar to other recurrent translocations involving 3q26, such as t(3;3) and t(3;21), the t(3;8)(q26;q24) is implicated not only in myelodysplastic syndrome and acute myeloid leukemia, but also in progression of chronic myeloid leukemia. These findings extend the known disease spectrum associated with this cytogenetic aberration.     

IGH gene involvement in two cases of acute lymphoblastic leukemia with t(14;14)(q11;q32) identified by sequential R-banding and fluorescence in situ hybridization

Translocation (14;14)(q11;q32) or inv(14)(q11q32) is a common cytogenetic aberration in T-cell leukemia associated with ataxia-telangiectasia (AT); however, rare reports have indicated that this abnormality also occurs in B-lineage acute lymphoblastic leukemia (ALL). We report here two cases with common-type ALL exhibiting the chromosomal aberration t(14;14)(q11;q32). The immunophenotype showed the blasts were positive for CD9, CD10, CD38, CD22, and CD15 in case 1 and positive for CD2, CD9, CD10, CD19, CD38, CD20, and CD22 in case 2, but negative for CD3, CD4, and CD8 expression in both cases. The cytogenetic analysis revealed del(6)(q22), and t(14;14)(q11;q32) in case 1 and t(14;14)(q11;q32),+mar in case 2. Fluorescence in situ hybridization (FISH) and sequential R-banding FISH assay with dual-color break-apart IGH probe confirmed that t(14;14)(q11;q32) involved the IGH gene in our cases. The results indicate that the t(14;14)(q11;q32) involving IGH at 14q32 in B-lineage ALL in our cases differ from those reported to involve the TCL1 gene on 14q32.1 in T-cell leukemia associated with AT. Sequential R-banding and FISH provide precise analysis of alterations of chromosomes and genes involved.     

Childhood myeloid/natural killer precursor acute leukemia with novel chromosomal aberrations der(5)t(4;5)(q31;q31.3) and t(14;17)(q32;q23)

We report a unique case of childhood acute leukemia. The leukemia blasts had lymphoblastoid appearance and expressed CD33, CD13, CD34, CD4, CD7, and CD56. The morphology and immunophenotype were most consistent with myeloid/natural killer precursor acute leukemia. The blasts had a complex karyotype, including two chromosomal aberrations, der(5)t(4;5)(q31;q31.3) and t(14;17)(q32;q23), not previously described in childhood acute leukemia. The patient achieved morphological remission following myeloid-based leukemia therapy.     

Philadelphia-like translocation t(9;22)(q34;q11) found in a follicular lymphoma involving not BCR and ABL but IGL-mediated rearrangement of an unknown gene on 9q34

In a case of follicular center cell lymphoma (FCCL) without evidence of histologic progression towards a high-grade lymphoma, t(9;22)(q34;q11) was found simultaneously with a t(14;18)(q32;q21) and a t(8;14)(q24;q32). Molecular studies of this case showed BCL2 and MYC rearrangements in addition to the rearrangements of immunoglobulin heavy (IGH) and lambda (IGL) loci. Investigation of the t(9;22) using Southern blot and RT-PCR analysis failed to detect M-bcr or m-bcr rearrangements of BCR. Two-color fluorescence in situ hybridization (FISH) with ABL and BCR probes revealed presence of a “fusion” signal, but its atypical localization [der(9)] and gene order [cen-ABL-BCR-tel] indicated that this translocation differed from the t(9;22) in chronic myeloid leukemia and did not involve either ABL or BCR. In addition, further FISH analysis using 9q34- and 22q11-specific probes localized the breakpoint on chromosome 9 distal to the NOTCH1 gene and the breakpoint on 22q11 in the IGL gene cluster. These results indicate an IGL-mediated rearrangement of an unknown gene at 9q34 that together with BCL2 and MYC might be involved in the lymphomagenesis of the present case of FCCL and perhaps in other cases of non-Hodgkin lymphoma in which t(9;22) is sporadically occurring. Genes Chromosomes Cancer 20:113–119, 1997. © 1997 Wiley-Liss, Inc.     

A case of papillary meningioma with a t(1;4)(q44;q21)

We report the results of cytogenetic analyses of three cases of meningiomas. The first case, a papillary meningioma, showed only one cytogenetic abnormality, 46,XX,t(1;4)(q44;q21). In contrast, the other two benign fibroblastic meningiomas showed loss of chromosome 22. Loss and/or rearrangement of chromosomes other than chromosome 22 appears to be associated with a more aggressive clinical course. It is suggested that a sole cytogenetic abnormality with a normal chromosome 22 indicates an atypical nature of meningioma.     

New complex t(2;11;17)(p21;q23;q11), a variant form of t(2;11), associated with del(5)(q23q32) in myelodysplastic syndrome-derived acute myeloblastic leukemia

The t(2;11)(p21;q23) is a rare recurrent aberration observed in myelodysplastic syndrome (MDS) and acute myeloblastic leukemia (AML). It has been suggested that t(2;11) is specifically associated with a deletion of the long arm of chromosome 5 (5q). A 63-year-old man was initially diagnosed as AML with del(5)(q23q32) as a sole abnormality. At relapse, t(2;11;17)(p21;q23;q11) in association with del(5q) appeared in 14 of 20 cells by G-banding. Spectral karyotyping confirmed three derivative chromosomes, der(11)t(2;11), der(17)t(11;17), and der(2)t(2;17). Fluorescence in situ hybridization analysis with a probe for MLL demonstrated that the breakpoint at 11q23 was telomeric to the MLL gene. Nine of 10 reported cases with t(2;11) and del(5q) had MDS including 5q- syndrome and four of them evolved to AML, as observed in the present case. Our results indicated that t(2;11;17) was a secondary genetic change, which appeared during disease progression after del(5q) was observed. Furthermore, considering another reported case, the MLL gene seems to be not involved in the pathogenesis of MDS/AML with t(2;11) and del(5q).