A new non-random chromosomal translocation t(3;6)(q27;p21.3) associated with BCL6 rearrangement in two patients with non-Hodgkin's lymphoma

We describe two cases of non-Hodgkin's lymphoma associated with t(3;6)(q27;p21.3) and BCL6 rearrangement. The first case was in a 78-year old woman, whose performance status (PS) was 1, the serum lactate dehydrogenase (LDH) level was elevated, and the Ann Arbor stage was IIIA with no extra nodal lymphomatous site. The pathological diagnosis from a biopsy of the inguinal lymph node was 'malignant lymphoma (ML), follicular, small cleaved' according to the Working Formulation. Complete remission was achieved. Although she had relapse in 1992, remission was obtained again. The second case was in a 62-year old man, whose PS was 1, the serum LDH was normal, and Ann Arbor stage was IVA with the involvement of the small intestine. Histological diagnosis of the cervical lymph node was 'ML, diffuse, large cell'. Complete remission was obtained without relapse. The 3q27 translocations, found in 20-30% of non-Hodgkin's lymphoma, are unique in having multiple chromosomal translocation partners. Chromosome band 6p21.3 is one of these partner sites that may be the site of a novel gene. The two cases presented here show that this translocation is a non-random chromosomal change involving 3q27 and BCL6. Since t(3;6) was the sole karyotypic abnormality in one case, this translocation may play a role in lymphomagenesis.     

A translocation t(8;14) and c-myc gene rearrangement associated with the histological transformation of B-cell acute lymphocytic leukemia (FAB-L2) into Burkitt''s type (FAB-L3) leukemia

During the late rainy season and winter season in 1990, outbreaks of suspected trypanosomiasis in native cattle (Bos indicus) occurred on 13 farms in Petchaboon province, Thailand. Forty-two cattle presented with nervous symptoms including circling, excitation, jumping, aggressive behavior, lateral recumbency, convulsion and finally death. Blood samples from 39 cattle on the two farms in which the outbreaks occurred were collected and examined for the presence of Trypanosoma evansi. It was found that all 16 blood samples from cattle on farm A were positive of T. evansi by mouse inoculation and indirect fluorescent antibody test (IFAT). In cattle from farm B, on the other hand only 37.5% and 39% of the samples were positive by mouse inoculation and IFAT, respectively. T. evansi was detected on impression smears of organs from the three cattle which died with nervous symptoms and also in smears made from their cerebrospinal fluid. In addition, trypanosomes were isolated from the cerebrum, cerebellum, pons and spinal cord by mouse inoculation.     

A de nevo complex t(7;13;8) translocation with a deletion in the TRPS gene region

Molecular cytogenetic analyses have resolved the pathogenetic aberration of an 8-year-old girl with tricho-rhino-phalangeal syndrome type I (TRPS I), normal intelligence, and a karyotype originally described as 46,XX,t(8;13)(q24;q21). R- and Q-banding and high resolution R-banding analyses have also disclosed a seemingly mosaic abnormality of the distal short arm of chromosome 7 but have not fully characterized this abnormality. Combined primed in situ labelling and chromosome painting, and three-colour chromosome painting have revealed a complex, apparently balanced translocation t(7;13;8). Fluorescence in situ hybridization with yeast artificial chromosome and cosmid clones from 8q24.1 has shown an interstitial deletion of at least 3 Mb covering most of the TRPS I critical region.     

Detection of a human chromosomal translocation t(8;9) in a baby with multiple malformations using two-color fluorescence in situ hybridization

In human fibroblast cultures TPA increased IL-6 and IL-8 production. This was reduced by vitamin D3 metabolites and analogs. The two analogs employed: 1,25 (OH)2-22 (E)-dehydro-24-monohomo vitamin D3 (Compound A) and 1,25 (OH)2 -22 (E)-dehydro-24 dihomo-vitamin D3 (Compound B) may be useful in the therapy of pathologic proliferative disorders including psoriasis, particularly since they are less toxic and have less effect on calcium metabolism than vitamin D3.     

A mild phenotype associated with der(9)t(3;9) (p25;p23)

A female infant is described with hypoglycaemia, hypotonia, obesity of the trunk and thighs, and mild dysmorphic features. Growth parameters were consistently above the 90th centile. Chromosome analysis showed her to have a derived chromosome 9 inherited from a maternal t(3;9)(p25;p23) by adjacent I segregation. She had features in common with both the dup(3p) and del(9p) syndromes. There are few reports of this chromosome rearrangement and the features are milder than expected for the degree of imbalance, complicated in males by sex reversal. The repeated reports of macrosomia may suggest an overgrowth syndrome.     

The t(14;18) in a patient with de novo acute lymphoblastic leukemia is associated with t(8;9)

Cytogenetic analysis of a bone marrow aspirate from a patient with acute lymphoblastic leukemia (ALL) revealed the presence of a complex karyotype containing the translocation, t(14;18)(q32;q21). Further investigations using fluorescence in situ hybridization (FISH) allowed the characterization of an additional translocation, t(8;9)(q24;p1?). The association of t(14;18)(q32;q21) and t(8;9)(q24;p13) has recently been described in two patients with de novo ALL (Nacheva et al. Blood 1993;82:231-240) and this report supports these findings.     

Detection of the chromosomal translocation t(11;14) by polymerase chain reaction in mantle cell lymphomas

The t(11;14)(q13;q32) and its molecular counterpart, BCL1 rearrangement, are consistent features of mantle cell lymphoma (MCL). Rearrangement is thought to deregulate the nearby CCND1 (BCL1/PRAD1) proto-oncogene, a member of the cyclin G1 gene family, and thereby to contribute to tumorigenesis. We and others have previously shown that the BCL1 locus is rearranged in 55% to 60% of MCL patients and that, on chromosome 11, more than 80% of the breakpoints are localized within a 1-kbp DNA segment known as the major translocation cluster (MTC). We have determined the nucleotide sequence for a portion of the MTC region, and constructed chromosome 11-specific oligonucleotides that were in conjunction with a consensus immunoglobulin (Ig) heavy chain joining region (JH) primer used to perform the polymerase chain reaction (PCR) to amplify t(11;14) chromosomal junctional sequences in DNA from 16 MCL patients with breakpoints in the MTC region. 15 of the 16 breakpoints that occurred at the MTC region were amenable to PCR detection. The sizes of the amplified bands, the existence or not of a Sac I site in the PCR products, and nucleotide sequencing of the amplified DNA from four patients showed that the breakpoints share a remarkable tendency to tightly cluster within 300 bp on chromosome 11, some of them occurring at the same nucleotide. On chromosome 14, the breakpoints were localized within the Ig JH. Our findings indicate that a BCL1 rearrangement can be detected using this approach in roughly one half of the MCL patients. This has implications for both the diagnosis and the clinical management of MCL.     

Non-Hodgkin''s lymphomas and myeloid disorders: deletions associated with t(2;5) and t(3;5) detected by FISH

Tubulovillous adenoma of the duodenum is a rare tumor. Almost all of the lesions have been reported endoscopically and are recognized as small, sessile, polypoid lesions. This article discusses an unusual case of pedunculated tubulovillous adenoma of the duodenum in a 48-yr-old woman. The lesion was discovered on the upper part of the descending duodenum during a gastric mass survey. The polyp was removed using an electrocautery snare and was histologically diagnosed as tubulovillous adenoma.     

Klinefelter syndrome associated with 13/14 translocation abnormality 46,XXY,t(13q;14q)

In this communication, a case of Klinefelter syndrome associated with a 13/14 translocation is described. Such a rare occurrence is most probably due to the de novo arrangement of chromosomes related to the advanced ages of both parents at conception.     

The LMO1 and LDB1 proteins interact in human T cell acute leukaemia with the chromosomal translocation t(11;14)(p15;q11)

The ectopic expression of LMO1 or LMO2 in T cell acute leukaemias resulting from chromosomal translocations t(11;14)(p15;qll) or t(11;14)(p13;q11) respectively in a causal factor in tumorigenesis. LMO1 has been found as a heterodimer with a 46 Kd protein in a T cell line derived from a childhood T-acute leukaemia. This 46 Kd protein is the LIM-binding protein LDB1/NLI. The latter is a phosphoprotein and binds to LMO1 in its phosphorylated state and essentially all the LMO1 and LDB1 protein in the T cell line is part of the complex. Therefore, the LMO1-LDB1 interaction is likely to be involved in tumorigenesis after LMO1 is ectopically expressed following chromosomal translocation in T cells prior to development of acute leukaemias.     

Successful treatment with idarubicin in a pediatric case of t(8;21) acute myelogenous leukemia with additional chromosomal abnormalities at relapse]

A 9-year old boy was admitted to our hospital due to a relapse of acute myelogenous leukemia (AML). A chromosomal analysis at the time of relapse revealed abnormalities in addition to 45, X,-Y, t(8;21) (q22;q22) when AML was first diagnosed. The patient was given granulocyte-colony stimulating factor (G-CSF), cytosine arabinoside (Ara-C) and aclarubicin (CAG therapy), but this treatment regimen was not effective. He was next treated with G-CSF (started 3 days prior to the administration of anticancer drugs), Ara-C, (200 mg/mm2 for 7 days), Etoposide (VP.16, 150 mg/mm2 for 5 days) and Idarubicin (8 mg/mm2 for 5 days) according to the modified Japan Cooperative Protocol ANLL 91 for children. Although his condition had been septic and he had experienced renal and respiratory failure, he achieved a complete remission after 140 days without additional therapy. The patient returned to a condition of health and received a bone marrow transplant from an unrelated donor. We concluded that this treatment regimen is effective for the relapse of AML in children.     

A new class of defective hepatitis B virus genomes with an internal poly(dA) sequence

Sequence heterogeneity of hepatitis B virus (HBV) is increasingly recognized to play a role in virus-host interaction. We have used a recently established method for HBV full-length genome amplification to search for novel types of HBV variants and to investigate further the sequence heterogeneity of HBV genome populations. Using this method, a substantial fraction of HBV genomes much shorter than wildtype size was found in some sera and liver biopsies from infected patients. Cloning and sequencing of a number of these HBV genomes as well as hybridization studies revealed a new minor class of HBV genomes with an internal poly(dA) sequence approximately 60 to more than 100 nucleotides long in 4 of 10 patients. The 5'-ends of the internal poly(dA) sequences are located at positions corresponding to the authentic processing/polyadenylation sites of the RNA pregenome, whereas the positions of the 3'-ends are variable due to different sizes of adjacent deletions. These data suggest that the poly(A) tail of the pregenomic RNA is occasionally reverse transcribed by the HBV P-protein and during this process a deletion seems to be introduced into the DNA minus strand. We propose a mechanism by which this could be accomplished during DNA minus strand synthesis.     

Familial C/D translocation t(9;13)(9p23.13q21) in a male associated with recurrent abortion

A familial reciprocal translocation, established by R-banding as t(9;13) (9p23;13q21), is described in a phenotypically normal male carrier, whose father is also a balanced carrier and wife had four consecutive spontaneous abortions. The role of translocation in reproductive failure through production of chromosomally unbalanced gametes or by impairment of the spermatogenesis is briefly discussed.