B-cell acute lymphoblastic leukemia with tandem t(14;14)(q11;q32).

Translocation (14;14)(q11;q32) was associated with acute lymphoblastic leukemia in a child. The B-cell lineage of the leukemic cells led us to perform FISH studies, which showed that the chromosomal breakpoints were telomeric to TCRA/D and IGH loci. These findings show that FISH analyses are necessary when unusual features are associated with a recurrent translocation.     

一例伴t(14;14)(q11;q32)易位的B细胞急性淋巴细胞白血病的临床和分子细胞遗传学研究

目的 报告1例伴t(14;14)(q11;q32)易位的罕见B细胞急性淋巴细胞白血病(B-lineage acute lymphoblastie leukemia,B-ALL)病例,阐明其临床和分子细胞遗传学特征.方法 分析1例伴t(14;14)(q11;q32)易位B-ALL患者的临床资料;将患者骨髓细胞24h培养后按常规方法制备染色体标本,采用R显带技术进行核型分析;分别应用IGH双色断裂点分离探针、CEBPE双色断裂点分离探针、4号全染色体涂染探针和ALL组合探针进行荧光原位杂交(fluorescence in situ hybridization,FISH)分析.结果 常规细胞遗传学分析显示患者核型为47,XX,+4,t(14;14)(q11;q32)[20],FISH分析进一步证实了这种核型异常.IGH双色断裂点分离探针FISH分析表明t(14;14)(q11;q32)易位累及IGH基因,CEBPE双色断裂点分离探针FISH分析提示t(14;14)(q11;q32)易位中IGH的伙伴基因为CEBPE基因.结论 在B-ALL中t(14;4)(q11;q32)易位同时累及IGH和CEBPE基因为少见的再现性遗传学异常,该异常可定义B-ALL中一种新的亚型.伴有t(14;14)(q11;q32) IGH/CEBPE易位的B-ALL患者可能预后较好.     

Infant acute lymphoblastic leukemia with t(11;16)(q23;p13.3) and lineage switch into acute monoblastic leukemia

Rearrangements of the mixed-lineage leukemia (MLL) gene have been associated with a poor prognosis in infant acute lymphoblastic leukemia (ALL). Previously, MLL translocations involving the CREP-binding protein (CREBBP) gene at chromosome band 16p13.3 have primarily been reported in treatment-related acute myeloid leukemia, after chemotherapy for other primary malignancies using topoisomerase II inhibitors. We report a case of de novo infant ALL with t(11;16)(q23;p13.3). After chemotherapy, this patient developed an acute monoblastic leukemia (M5b) with retention of the t(11;16)(q23;p13.3), indicating that this is a lineage switch of the original leukemic clone. To our knowledge, these findings have not been previously reported.     

t(11;19)(q23;p11) in a child with acute T-cell leukemia

A translocation, t(11;19)(q23;p11), is reported in a child with T-cell leukemia. Our case indicates that the t(11;19) may not be restricted to the monocytic leukemias, as earlier reported, but may occur in other malignancies.     

A translocation t(9;11)(p11;q23) in T-cell acute lymphoblastic leukemia (FAB-l2)

We here report a t(9;11)(p11;q23) as the only abnormality in the affected cells of a 20-year-old male with acute lymphoblastic leukemia (L2) of T-cell origin. One hundred six patients with acute leukemia and involvement of band 11q23 were reviewed. Young age, hyperleukocytosis, and poor prognosis characterized almost all the cases in the acute leukemias with the 11q23 translocation, despite involvement of different recipient chromosomes and different morphologic and immunologic phenotypes.     

Characterization of the breakpoint of a t(14;14)(q11.2;q32) from the leukemic cells of a patient with T-cell acute lymphoblastic leukemia

The leukemic cells and derivative cell line from a 74-year-old male with T-cell acute lymphoblastic leukemia showed chromosomal abnormalities including a t(14;14)(q11.2;q32). This translocation is characteristic of a variety of T-cell malignancies, particularly T-cell prolymphocytic leukemia and the clonal proliferations of peripheral T cells in patients with ataxia-telangiectasia. Using DNA probes that spanned the T-cell receptor alpha chain (TCRA) joining (J) locus, the DNA rearrangement caused by the translocation was identified, cloned, and sequenced. The breakpoint shows site-specific juxtaposition of a TCRA joining segment and DNA from a region of 14q32 centromeric to the immunoglobulin heavy chain locus. Comparison of restriction map and nucleotide sequence from this translocation with other related chromosomal breakpoints suggests a dispersion of breakpoints throughout the 14q32 region.     

Spontaneous expression of fra(11)(q23) in a patient with Ewing's sarcoma and t(11;22)(q23;q11)

Cytogenetic analysis of a Ewing's sarcoma revealed a 46,XX,t(8;18)(q11;q21.3), t(11;22)(q23–24;q11–12) chromosome pattern. Observation of t(11;22) is consistent with other reported cases of Ewing's sarcoma. One breakpoint in this translocation, 11q23, coincides with the location of a folate-sensitive fragile site. Examination of peripheral blood leukocyte chromosomes from the patient revealed a 46,XX chromosome pattern with spontaneous, fluorodeoxyuridine-, and Bactrim-induced expression of fra(11)(q23). This may be the first demonstration of constitutional fra(11)(q23) expression in a patient with a neoplasm that exhibits a chromosome rearrangement involving this breakpoint and the first observation of spontaneous expression of this fragile site. These results provide a basis for discussion of the relationship between fragile sites and chromosome rearrangements.     

A complex genetic rearrangement in a t(10;14)(q24;q11) associated with T-cell acute lymphoblastic leukemia.

The t(10;14)(q24;q11) is observed in the leukemia cells of 5-10% of cases of T-cell acute lymphoblastic leukemia (T-ALL). Recently, molecular analyses of a number of these translocations revealed simple reciprocal translocations between the T-cell receptor delta chain gene (TCRD) and a region of 10q24. We have characterized, at the molecular level, a t(10;14)(q24;q11) in a patient with T-ALL. The translocation in this case, in contrast to the previous cases, is part of a complex genetic rearrangement. In addition to a reciprocal translocation between the D delta 3 gene segment of TCRD and a region of 10q24, a local inversion occurred within TCRD, involving the D delta 2 and V delta 2 gene segments. As a consequence, the entire joining and constant regions and most of the diversity regions of TCRD are located on the derivative 14 chromosome, whereas the joining and constant regions of TCRA are positioned on the derivative 10 chromosome. The chromosome 10 breakpoint in our patient, as in other t(10;14), clusters within a 9 kb breakpoint region. The occurrence of seven breakpoints within a localized region of chromosome 10 implies the existence of a nearby gene whose activation may have conferred a selective advantage on the leukemia cells. Moreover, as in the previous cases, the translocation in the present study exhibits recombination signal sequences or signal-like sequences adjacent to the breakpoint junction. The presence of such motifs suggests the involvement of the recombinase enzyme system in the generation of this genetic alteration.     

t(2;14)(q23;q32.3) as the sole abnormality in a patient with acute nonlymphocytic leukemia (FAB-M4)

Cytogenetic analysis of bone marrow cells from a 53-year-old man with acute nonlymphocytic leukemia (FAB-M4) revealed a t(2;14)(q23;q32.3) as the sole cytogenetic abnormality. This is the first report of a t(2;14)(q23;q32.3) as the sole abnormality in acute nonlymphocytic leukemia (M-4). The findings are discussed in relation to the possible role of genes located at 2q23 in acute nonlymphocytic leukemia.     

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.     

MLL is involved in a t(2;11)(p21;q23) in a patient with acute myeloblastic leukemia

We describe a patient with acute myeloblastic leukemia (AML‐M0) whose cells had a t(2;11)(p21;q23). Fluorescence in situ hybridization analysis with a probe for MLL showed that it was split, hybridizing to both the derivative 2 and 11 chromosomes. Nineteen other patients with 2p;11q translocations have been described; breakpoints in 14 of these are the same as in the case we describe. The phenotype of these patients is quite variable, with 14 patients having myelodysplastic syndrome which evolved to AML in six. Four patients had AML and two had acute lymphoblastic leukemia. MLL status has been studied in two other patients; one had MLL rearranged and one did not. Genes Chromosomes Cancer 24:151–155, 1999. © 1999 Wiley‐Liss, Inc.     

t(9;11)(p22;q24) in a patient with acute monocytic leukemia

A case of t(9;11)(p22;q24) in a patient with acute monocytic leukemia is described. The difficulties of establishing the precise breakpoints involved in this emerging association are discussed.     

Therapy-related acute myeloid leukemia with t(2;11)(q37;q23) after treatment for osteosarcoma

The survival rate for children with osteosarcoma (OS) has improved dramatically with the introduction of multiagent chemotherapy. As the number of pediatric cancer survivors increases, there is a concern about the development of secondary malignant neoplasms. Secondary acute myeloid leukemia (AML) has been rarely reported after treatment for OS. We describe a 14-year-old boy with OS of the left ileum who developed secondary AML 15 months after completion of treatment. Cytogenetic analysis of the leukemic cells demonstrated deletion 11q23, whereas fluorescence in situ hybridization revealed rearrangement of the MLL gene. Only the addition of the long-distance inverse polymerase chain reaction technique identified the SEPT2 as the MLL fusion partner resulting in t(2;11)(q37;q23) that was reported in a very few secondary AML cases. Because of the cryptic nature of MLL translocations that cannot be detected by conventional cytogenetics or may misinterpreted as deletion, additional molecular techniques are required to identify the precise translocation partner. Because long-distance inverse polymerase chain reaction is not available in most molecular laboratories, the true incidence of t(2;11)(q37;q23) and the involvement of SEPT2 as the MLL translocation partner could be more prevalent in secondary AML.     

Reciprocal translocation (11;19)(q23;p13) in congenital acute lymphoblastic leukemia

The cytogenetic, clinical, and immunologic findings ina 4-month-old girl with acute lymphoblastic leukemia (ALL) are reported. The malignant lymphoblasts were characterized cytogenetically by the reciprocal translocation t(11;19)(q23;p13); immunologically by an immature pre-B-ALL phenotype. In spite of the high-risk nature of the leukemia, the patient attained complete remission relatively quickly and is still free of disease 3 years after diagnosis. Because the only two previously reported ALL patients with t(11;19) also seem to have responded well to therapy, this cytogenetic abnormality might turn out to be an indicator of favorable prognosis in ALL.     

MLL-CBP fusion transcript in a therapy-related acute myeloid leukemia with the t(11;16)(q23;p13) which developed in an acute lymphoblastic leukemia patient with Fanconi anemia

We describe a boy with Fanconi anemia (FA) who developed acute lymphoblastic leukemia (ALL) (FAB-LI) followed by acute myeloid leukemia (AML) (FAB-M5) at relapse. The patient was diagnosed with early pre-B-cell ALL without preceding aplastic anemia and was treated with ALL-oriented chemotherapy which included doxorubicin (a total dose of 140 mg/m(2) administered), which is a topoisomerase II inhibitor. Complete remission was obtained, but after 38 weeks AML developed. The karyotype of ALL cells at diagnosis showed 46,XY, and that of AML cells at relapse was 46,XY, t(11;16)(q23;p13). An MLL gene rearrangement and MLL-CBP chimeric mRNA were found in AML, but not in ALL. A diagnosis of FA was confirmed by an increased number of chromosomal breaks and rearrangements in peripheral blood lymphocytes cultured with mitogen in the presence of mitomycin C. We conclude that this FA patient developed ALL followed by a therapy-related t(11;16)-AML resulting in an MLL-CBP fusion. Further examination of such patients would shed light on leukemogenesis in FA patients. Genes Chromosomes Cancer 27:264-269, 2000.