A der(22)t(9;22)(p13;q11) in bone marrow cells of a patient with multiple myeloma: a variant of the t(9;14)(p13;q32) associated with a subset of lymphoplasmacytoid lymphoma

An adult cattle egret (Bubulcus ibis) caught in Kobe of Hyogo Prefecture, Japan, in December 1995 died of a severe infection associated with the trematode parasite Pegosomum sp. At necropsy, 22 trematode parasites were found in the lumen of the bile duct, and the duct wall was markedly thickened. Histopathologically, severe cholangitis and cholecystitis were observed in close association with the parasites in the bile duct. Severe Pegosomum sp. infection may be one of the factors contributing to the mortality of wild cattle egrets. This is the first reported case of the genus Pegosomum infection in wild birds of Japan.     

High incidence of translocations t(11;14)(q13;q32) and t(4;14)(p16;q32) in patients with plasma cell malignancies

Abnormalities involving the 14q32 region are recurrent chromosomal changes in plasma cell malignancies. Recent preliminary molecular analyses found IGH rearrangements in almost 100% of human myeloma cell lines and in 75% of patients. However, no systematic study analyzing the nature of the partner chromosomal regions have been reported thus far. To define the exact incidence of illegitimate IGH rearrangements and the respective incidence of partner genes cloned to date, we analyzed 141 patients with either multiple myeloma (MM, n = 127) or primary plasma cell leukemia (PCL, n = 14) using fluorescence in situ hybridization. The overall incidence of illegitimate recombinations was 57% (80 of 141 patients). Analysis of this incidence according to Durie and Salmon stage, patients' status, i.e., MM versus primary PCL and diagnosis versus relapse, immunoglobulin type and subtype, and beta2-microglobulin value, did not show any correlation. To analyze the nature of the partner chromosomal region, we selected probes specific for the following genes: FGFR3 (4p16), MYC (8q24), CCND1 (11q13), MAF (16q23), and BCL2 (18q21). These probes, combined with differentially labeled 14q32 probes, were used for dual-color fluorescence in situ hybridization on interphase plasma cells. Among the 80 patients with illegitimate IGH rearrangement, we identified 23 IGH-CCND1 fusion cases [i.e., t(11;14)], 17 IGH-FGFR3 fusion cases [i.e., t(4;14)], 3 IGH-MYC fusion cases [i.e., t(8;14)], and only one IGH-MAF fusion case. No IGH-BCL2 fusion case was detected. In 37 of 80 patients, none of these partner genes was involved. Analysis of cases with specific translocations according to their bioclinical features at diagnosis did not show any correlation. This study demonstrated that CCND1 and FGFR3 genes are involved together in about 50% of MM and primary PCL patients with illegitimate IGH rearrangements.     

A case of pigmented dermatofibrosarcoma protuberans (Bednar tumor)

The present paper reports a 67-year-old male with pigmented dermatofibrosarcoma protuberans (Bednar tumor) on his right shoulder. The lesion had recurred twice. Clinically, the lesion was a reddish-brown, exophytic, multilobular, firm nodule with an irregular surface, which measured 6.4 x 4.2 cm. Histologically, the proliferated fibroblasts showed a cartwheel pattern and stained positively with CD34, similar to those of a common dermatofibrosarcoma protuberance. However, many melanin-bearing cells that were positive for the S-100 protein were found intermingled among the tumor cells. Based on these findings, we concluded that the clinical manifestations, level of malignancy, and cytological features, as well as the exception of melanin-bearing dendritic cells associated with pigmented dermatofibrosarcoma protuberans, suggest a common dermatofibrosarcoma protuberans. This supports the hypothesis that pigmented dermatofibrosarcoma protuberans is a pigmented variant of dermatofibrosarcoma protuberans. Thus, this type of tumor is not benign, but is an intermediate malignant tumor.     

Fifty-one patients with acute myeloid leukemia and translocation t(8;21)(q22;q22): an additional deletion in 9q is an adverse prognostic factor

The translocation t(8;21)(q22;q22) occurs in 6 to 12 percent of patients with AML, and usually predicts a good response to chemotherapy with a high remission rate and a relatively long median survival. The influence of additional chromosome aberrations on the clinical outcome of patients with t(8;21) is unclear. We analyzed 51 cases of acute myeloid leukemia carrying a translocation t(8;21)(q22;q22); 23 female and 28 male patients. The complete remission rate was 92 percent and median overall survival was 52.4 months. The median overall survival of female patients was significantly worse than of male patients (37.2 months vs not reached, P = 0.025). Additional chromosome aberrations were detected in 41 patients at diagnosis (80 percent), 31 (61 percent) had lost a sex chromosome, seven (14 percent) showed a partial deletion of the long arm of chromosome 9 and in three patients (6 percent) a gain of chromosome 8 was observed. Whereas the loss of a sex chromosome had no influence on prognosis, a partial deletion of the long arm of chromosome 9 was an unfavorable prognostic factor. The median overall survival of the seven patients with del(9q) was only 12.5 months and thus significantly shorter than in patients with only t(8;21) or with t(8;21) and additional sex chromosome loss (median survival not reached: P = 0.0010).     

Severe aplastic anaemia in association with a unique constitutional translocation 46,XY,t(6;10)(q13;q22)c

Severe aplastic anaemia (SAA) is an uncommon disorder which may be associated with several congenital syndromes. However, it has rarely been described in association with a constitutional karyotypic abnormality. The breakpoint of the balanced t(6:10)(q13:q22) translocation described here does not disrupt any currently recognized gene of haemopoietic or stromal importance. This report also highlights the problems inherent in the use of bone marrow transplantation (BMT) for treating multiply transfused aplastic anaemia patients.     

Pediatric primary diffuse large cell lymphoma of bone with t(3;22)(q27;q11)

PURPOSE: A child with a primary lymphoma of bone (PLB) with a t(3;22)(q27;q11) is described. METHODS: An 11-year-old boy had a 5-week history of back pain and a destructive lesion of S1 that contained an epidural component. Histologic evaluation of a biopsy confirmed the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Karyotypic analysis disclosed a t(3;22)(q27;q11), but the amount of tumor tissue was insufficient for molecular studies of the BCL-6 gene. RESULTS: The patient remains free of disease 4 years after completion of intensive systemic chemotherapy and intrathecal chemotherapy. CONCLUSIONS: The lymphoma in the patient described in this report is highly unusual because of the coexistence of pediatric PLB and a t(3;22)(q27q11).     

A case of primary splenic large cell lymphoma with a t(9;14)(p13;q32)

Appropriately substituted 2,3-dihydro-7H-thiazolo[3,2-a]pyrimidin-7-ones 9-12 and 18 were considered as annulated analogues of HEPT (1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)-thymine), and some of these compounds were also found active against HIV-1, the most active one being 2,3-dihydro-5-[(3,5-dimethylphenyl)methyl]-3-ethoxy-6-ethyl-7H- thiazolo[3,2-a]pyrimidin-7-one (10b). S-Alkylation of 5-alkyl-6-(arylmethyl)-2-thiouracils 1-4 was performed with 2-bromoacetaldehyde acetals to furnish the S-[bis(alkoxy)ethyl] derivatives 5-8 and with allyl bromide to furnish S-allyl derivatives 17. The target compounds 9-12 were obtained by an N1 regioselective intramolecular cyclization reaction of silylated 5-8 using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the catalyst. Treatment of the S-allyl derivatives 17 with bromine in dry methylene chloride afforded the 3-(bromomethyl) derivatives 18.     

Molecular characterization of a variant Ph1 translocation t(9;22;11) (q34;q11;q13) in chronic myelogenous leukemia (CML) reveals the translocation of the 3'-part of BCR gene to the chromosome band 11q13

We performed cloning and sequence analysis of translocation junctions at 11q- and 22q- (Ph1) chromosomes and the corresponding germline DNAs of a variant Ph1-positive CML with t(9;22;11)(q34;q11;q13). Southern blot analysis using probes for different regions of bcr mapped the translocation break near the 5'-side of bcr exon 4. Cloning, Southern blot analysis and restriction map analysis of both bcr fragments showed that the part of bcr 3'- to the translocation break moved to 11q13. Sequence analysis of the translocation junction on the Ph1 chromosome showed that the translocation break occurred 63 bp upstream of exon 4. Compared to the germline sequence, bcr sequence from the translocated partners showed deletion of seven basepairs at the site of translocation. A probe derived from the 5'-region of the clone isolated from the 11q- chromosome identified clonal rearrangements in the leukemic DNA. Restriction map and sequence analysis showed that this clone consisted of the 3'-half of the glutathione S-transferase Pi (GST-Pi) gene and the 3'-part of bcr. We identified two point mutations in the GST-Pi allele involved in translocation. Northern blot analysis showed that the GST-Pi gene was expressed in the leukemic cells at blast crisis but not at chronic phase; however, no fusion mRNA between GST-Pi and bcr was identified. We did not find any sequence homology between 11q13 DNA and 22q11 DNA around the translocation breakpoints; however, sequences homologous to ALU repeats were identified close to the sites of translocation breaks at 22q11 and 11q13. This study supports our hypothesis that variant Ph1 translocations may occur as primary cytogenetic changes similar to the classical Ph1 translocations.     

Expression of the neural cell adhesion molecule CD56 is associated with short remission duration and survival in acute myeloid leukemia with t(8;21)(q22;q22)

Although acute myeloid leukemia (AML) with t(8;21) (q22;q22) is associated with a high complete remission (CR) rate and prolonged disease-free survival, treatment outcome is not universally favorable. Identifying factors that predict for treatment outcome might allow therapy to be optimized based on risk. AML with t(8;21) has a distinctive immunophenotype, characterized by expression of the myeloid and stem cell antigens CD13, CD15, CD34, and HLADr, and frequent expression of the B-cell antigen CD19 and the neural cell adhesion molecule CD56, a natural killer cell/stem cell antigen. Because CD56 expression has been associated with both extramedullary leukemia and multidrug resistance, we sought to correlate CD56 expression with treatment outcome in AML with t(8;21). Pretreatment leukemia cells from 29 adult de novo AML patients with t(8;21) treated on Cancer and Leukemia Group B (CALGB) protocols were immunophenotyped by multiparameter flow cytometry as part of a prospective immunophenotyping study of adult AML (CALGB 8361). CD56 was expressed in 16 cases (55%). There was no correlation between CD56 expression and age, sex, white blood cell count, granulocyte count, the presence of additional cytogenetic abnormalities, or the presence of extramedullary disease at diagnosis. The CR rate to standard-dose cytarabine and daunorubicin was similar for cases with and without CD56 expression (88% v 92%; P = 1.0). Post-CR therapy included at least one course of high-dose cytarabine in 24 of 26 patients who achieved CR; numbers of courses administered were similar in cases with and without CD56 expression. Although post-CR therapy did not differ, CR duration was significantly shorter in cases with CD56 expression compared with those without (median, 8.7 months v not reached; P = .01), as was survival (median, 16.5 months v not reached; P = .008). We conclude that CD56 expression in AML with t(8;21) is associated with significantly shorter CR duration and survival. Our results suggest that CD56 expression may be useful in stratifying therapy for this subtype of AML.     

Mosaicism for a tandem duplication dup(1)(q12q22) in an 18 year old female

We report a case of ventricular fibrillation with subacute myocarditis as the only underlying pathological abnormality in a 9-year-old child. The patient died suddenly after a follow-up of 13 years, despite the apparent control of the arrhythmia.     

Translocation (13; 18) (q22; p 11) and prenatal diagnosis (author's transl)

A balanced translocation (13; 18) (q 22; p 11) was diagnosed in two generations. Out of 10 pregnancies in these two translocation carriers, mother and daughter, only two phenotypically normal childern were born. One of these, namely the daughter, showed balanced translocation, whilst a normal karyotype was diagnosed prenatally in the second case. The other eight pregnancies ended either in spontaneous abortions, in intrauterine death or in lethal malformations. In the present translocation the formation of unbalanced gametes seems to be enhanced.     

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.