Philadelphia chromosome positive precursor B-cell acute lymphoblastic leukemia with a translocation t(2;14)(p13;q32)

A female patient with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) was analyzed cytogenetically. Karyotyping of the leukemic cells showed a Philadelphia chromosome (Ph1), and also showed a translocation between 2p13 and 14q32, which is thought to be specific for children with B-cell chronic lymphocytic leukemia. DNA analysis with both conventional and pulsed-field gel electrophoresis revealed the rearrangement of the c-abl gene, the BCR gene outside the 5.8 kb breakpoint cluster region (bcr or M-BCR), and the comigration of an abnormal Not I pHabl 5' and 3'-bcr fragment, indicating the presence of BCR/c-abl recombination. The JH gene was rearranged, but the JK gene showed a germline configuration, as with previously reported cases with a t(2;14). This case is the first report of a patient with Ph1-positive precursor B-ALL, in whom a specific translocation t(2;14)(p13;q32) is found simultaneously.     

The t(10;11)(p14;q21) translocation in three children with acute myeloblastic leukemia

A total of 161 cases of pediatric de novo acute myeloblastic leukemia (AML) have been reviewed, for which complete karyotyping was available and three cases (2%) were identified with t(10;11)(p14;q21). Two of the three children were infants with monoblastic (FAB M5) leukemia and the third was an adolescent with undifferentiated myeloid (FAB M1) leukemia. Both infants presented with increased levels of lactate dehydrogenase. None of these cases had increased eosinophils. One of the infants is in remission 18+ months after diagnosis and intensive chemotherapy; the two other children attained brief initial remissions but succumbed to their disease within 11 months of diagnosis. The prognosis of such children appears to be similar to that of cases of AML lacking this translocation.     

Cloning of the t(11;14)(q13;q32) translocation breakpoints from two human leukemia cell lines

The t(11;14)(q13;q32) translocation has been associated with several subtypes of human leukemia and lymphoma. It has been proposed that this translocation activates a proto-oncogene designated BCL1. In an effort to better understand the mechanism by which this translocation leads to malignancy, we have studied this translocation in two human cell lines. MO1094 and MO2058 were derived from patients with prolymphocytic variants of chronic lymphocytic leukemia. Southern blotting of the MO2058 cell line documented that the translocation linked the Jh region in the immunoglobulin heavy chain gene to the previously described BCL1 major translocation cluster (MTC). Using the polymerase chain reaction, we cloned this translocation and showed that the chromosome 11 breakpoint was within 7 bp of two other samples reported previously. Southern blotting of the MO1094 cell line suggested that the translocation in this cell line might link Jh sequences to a new region in the BCL1 locus on chromosome 11. Therefore, the MO1094 breakpoint was cloned from a genomic library. Comparison with normal cloned DNA from the BCL1 locus showed that the chromosome 11 breakpoint occurred 24 kb telomeric of the MTC. This work reinforces the concept that translocation breakpoints in the BCL1 locus are scattered over at least 63 kb.     

Clinical significance of the translocation (11;14)(q13;q32) in multiple myeloma

The most common chromosomal translocation in multiple myeloma (MM) is t(11;14)(q13;q32). Here, we describe the clinical characteristics of patients with MM who have this translocation. We have identified 24 patients at our institution who had t(11;14)(q13;q32) as determined by standard cytogenetic analysis (CC). Seven patients had the translocation detected at the time of original diagnosis and 17 at the time of relapse. Median survival in all patients after original diagnosis was 43 months; median survival after the translocation was detected was 11.9 months. Four patients had a clinical diagnosis of plasma cell leukemia. Most patients had an elevated beta2-microglobulin (13/20 had >4 microg/ml). The bone marrow (BM) labeling index (LI) of patients, at the time of translocation detection, was elevated in most (median 1.4%, 17/23 patients had BMLI > or = 1%). Of the 24 patients, 19 (79%) died of disease progression and 5 (21%) were alive with disease at last follow-up. Lytic lesions, bone pain, or compression fractures eventually developed in all patients. Patients with MM who have t(11;14)(q13;q32) detected by standard cytogenetics seem to have an aggressive clinical course.     

Bcl-3/IgH translocation (14;19)(q32;q13) in non-Hodgkin's lymphomas

The recurrent cytogenetic (CG) abnormality t(14;19)(q32;q13) involving the oncogene BCL3 is described in patients with atypical chronic lymphocytic leukemia (CLL). We report four patients with non-Hodgkin's lymphoma (NHL) bearing t(14;19). All cases were female and their age ranged from 62 to 91. Histologically, there were two cases of small lymphocytic lymphoma (SLL), both CD11c positive with atypical morphology, one case of Burkitt like lymphoma (BLL), and one case of diffuse large cell lymphoma (DLC-L). One SLL patient showed t(14;19) as the sole abnormality and experienced a benign course for 8 years. The other three cases showed secondary CG progression, including tetraploidy, del(6q), t(8;22) and del(13q). These cases were aggressive in clinical behavior, including an SLL case which transformed to DLC lymphoma in 4 months. Southern analysis and long distance PCR confirmed BCL3/IgH Calpha translocation in one case. We propose that NHLs with t(14;19) may have evolved from the same spectrum of disease as atypical CLL. The poor prognosis of t(14;19) disease is associated with the occurrence of recurrent secondary CG changes, commonly found in B cell lymphoproliferative diseases.     

Complex karyotype including chromosomal translocation (8;14) (q24;q32) in one case with B-cell prolymphocytic leukemia

We report a case of a 64-year-old white female patient, who presented with symptomatic anemia (Hgb: 6.8g/dl), thrombocytopenia (platelets: 94,000/mcl) and leukocytosis (WBC: 156,000/mcl). Peripheral blood smear revealed markedly increased white blood cell count with predominance of atypical lymphoid cells of intermediate size, moderately dense chromatin, and prominent large single nucleoli. Bone marrow aspirate smear showed predominance (78%) of atypical lymphoid cells morphologically identical to those seen in the peripheral blood. The bone marrow core biopsy was hypercellular and packed with prominent infiltrate of prolymphocytes. Immunophenotypic analysis revealed a population of monoclonal cells (75% of all -erythroid cells) characterized by CD45+, CD19+, CD20+, CD5+, HLA-DR+, CD10-, CD23+/-, CD38+ and FMC7-. The abnormal cells were restricted to kappa light chain immunoglobulin with low intensity. Cytogenetic study showed an abnormal clone of eight cells with the following karyotype: 45,X,-X,add(8)(p11.2),t(8;14)(q24;q32),add(20)ql3[8]/46,XX[12]. The relative rarity of B-PLL and the heterogeneity of clinical and laboratory parameters make it difficult to define the natural history and prognosis in all cases. The optimal treatment for B-PLL is still unknown and to date there are no reports of chromosomal abnormalities as a prognostic factor. The patient was treated with six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Complete remission was achieved according to the criteria defined by National Cancer Institute Working Group for CLL.     

Childhood acute leukemia with t(11;19) (q23;p13).

From 583 cases of acute lymphoblastic leukemia (ALL) and 181 cases of acute myeloid leukemia (AML) in childhood, seven patients were identified to have t(11;19) (q23;p13) by sequential cytogenetic analyses. The t(11;19) was associated with B-precursor ALL at diagnosis in three patients and at relapse in one patient. All four tested patients with B-precursor failed to express the CD10 antigen when the t(11;19) was detected, and one of three patients tested expressed myeloid-associated markers. In three other patients the translocation was detected either at lineage conversion from ALL to M5 AML (n = 2) or from AML to CD10- B-precursor ALL (n = 1). Leukemic blasts of four patients had an entirely different karyotype at the time of lineage conversion or loss of CD10 expression, suggesting an induction of a second neoplasm. Thus the t(11;19) can be found in de novo or secondary acute leukemia with lymphoid (CD10-) or myeloid (monoblastic) phenotype. Further investigation of the gene(s) involved in the 11q23 chromosomal region and the breakpoints in the 19p13 region is needed to understand the leukemogenesis of this apparently heterogeneous group of disorders.     

Hemophagocytic syndrome complicating T-cell acute lymphoblastic leukemia with a novel t(11;14)(p15;q11) chromosome translocation

A case of hemophagocytic syndrome that developed in a patient with T-cell acute lymphoblastic leukemia (ALL) with a novel chromosome translocation involving 14q11 is reported. A 15-year-old boy with T-cell ALL in relapse showed leukemic cells with an abnormal karyotype of 46,XY,-15,t(11;14)(p15;q11), +der(15)t(15;?)(p11;?). Pancytopenia and extensive hemophagocytosis by macrophages in the bone marrow were observed after reinduction chemotherapy and again at the terminal stage. At autopsy, infiltration of such cells was also found in other organs. The findings suggested occurrence of hemophagocytic syndrome probably associated with cytomegalovirus (CMV) infection. The t(11;14)(p15;q11) may be a novel translocation specific for T-cell ALL, and conceivably, the association of T-cell ALL with the histiocytosis in this patient may not have been coincidental.     

多发性骨髓瘤中14q32易位与13q14缺失的相关性研究

目的 研究多发性骨髓瘤(MM)常见的分子遗传学异常14q32易位与13q14缺失及其与临床指标的关系.方法 采用间期荧光原位杂交(I-FISH)技术应用RB1、D13S319和LSI IGHC/IGHV探针检测49例MM患者骨髓标本中RB1基因、13q14.3缺失及14q32易位,结合临床资料作统计分析.结果 49例MM患者有26例(53.1%)检测到14q32易位,25例(51.02%)存在13q14缺失(其中18例检测到13q14.3缺失,9例存在RB1缺失).Spearman相关分析显示,14q32易位多见于浆细胞比例高的患者(r=0.316,P=0.27),与患者年龄、国际分期系统(ISS)分期、免疫球蛋白分型、β2微球蛋白及肾损害无相关性(P＞0.05).结论 13q14缺失及14q32相关的易位在MM中发生率均较高,两者有密切相关性;14q32易位的MM患者浆细胞百分比明显升高,14q32易位的检测可作为预测MM预后的指标.     

多发性骨髓瘤中14q32易位与13q14缺失的相关性研究

目的 研究多发性骨髓瘤(MM)常见的分子遗传学异常14q32易位与13q14缺失及其与临床指标的关系.方法 采用间期荧光原位杂交(I-FISH)技术应用RB1、D13S319和LSI IGHC/IGHV探针检测49例MM患者骨髓标本中RB1基因、13q14.3缺失及14q32易位,结合临床资料作统计分析.结果 49例MM患者有26例(53.1%)检测到14q32易位,25例(51.02%)存在13q14缺失(其中18例检测到13q14.3缺失,9例存在RB1缺失).Spearman相关分析显示,14q32易位多见于浆细胞比例高的患者(r=0.316,P=0.27),与患者年龄、国际分期系统(ISS)分期、免疫球蛋白分型、β2微球蛋白及肾损害无相关性(P＞0.05).结论 13q14缺失及14q32相关的易位在MM中发生率均较高,两者有密切相关性;14q32易位的MM患者浆细胞百分比明显升高,14q32易位的检测可作为预测MM预后的指标.     

多发性骨髓瘤中14q32易位与13q14缺失的相关性研究

 目的　研究多发性骨髓瘤（MM）常见的分子遗传学异常14q32易位与13q14缺失及其与临床指标的关系。方法　采用间期荧光原位杂交（I-FISH）技术应用RB1、D13S319和LSI IGHC／IGHV探针检测49例MM患者骨髓标本中RB1基因、13q14.3缺失及14q32易位,结合临床资料作统计分析。结果　49例MM患者有26例（53.1 %）检测到14q32易位,25例（51.02 %）存在13q14缺失（其中18例检测到13q14.3缺失,9例存在RB1缺失）。Spearman相关分析显示,14q32易位多见于浆细胞比例高的患者（r＝0.316,P＝0.27）,与患者年龄、国际分期系统（ISS）分期、免疫球蛋白分型、β2微球蛋白及肾损害无相关性（P＞0.05）。结论　13q14缺失及14q32相关的易位在MM中发生率均较高,两者有密切相关性;14q32易位的MM患者浆细胞百分比明显升高,14q32易位的检测可作为预测MM预后的指标。     

Gene rearrangement and overexpression of PRAD1 in lymphoid malignancy with t(11;14)(q13;q32) translocation.

The proto-oncogene PRAD1 (parathyroid adenoma 1) on chromosome 11q13 was found to be overexpressed in all five B-cell lines with t(11;14)(q13;q32) translocation tested. One B-cell lymphoma and four myeloma cell lines with this translocation demonstrated more than 10-fold overexpression as determined by Northern blot analysis, when compared with normal lymphoid tissues such as thymus, spleen and lymph node. Hematopoietic cell lines without the translocation were also examined, but none of these demonstrated the overexpression, confirming that overexpression of the PRAD1 gene is associated with t(11;14) translocation. A truncated form of mRNA was seen in one of five cell lines with the translocation, SP-49. Hybridization with different regions of the PRAD1 cDNA revealed that the truncated form of mRNA retained the coding region but had lost the 3' untranslated region. Southern blot analysis demonstrated a gene rearrangement in this SP-49 cell line. To study the genetic alteration responsible for the truncated form of mRNA in this cell line, the rearranged allele as well as the germline allele were cloned. The restriction map revealed that the rearranged portion was at the 3' end of the PRAD1 gene, eliminating the mRNA-destabilizing signal AUUUA. Human-rodent hybrid cell analysis demonstrated that the region introduced 3' of PRAD1 was derived from chromosome 11, suggesting that the PRAD1 gene region is deleted at the 3' end. Over-expression of the PRAD1 gene in association with t(11;14)(q13;q32) translocation suggested that in these cases the regulation of PRAD1 was altered by the juxtaposed gene, most likely the immunoglobulin heavy-chain gene from chromosome 14.     

Acute myeloblastic leukemia with t(8;21) following Philadelphia positive acute lymphoblastic leukemia

A patient with Philadelphia positive (Ph'+) acute lymphoblastic leukemia (ALL), in remission for over 4 years, developed an acute myeloblastic leukemia (AML), M2-type. During the second disease, the blast cells displayed a typical t(8;21)(q22;q22) translocation, in the absence of the Ph' chromosome. This is the first observation in the same patient of two leukemias displaying different cell phenotypes and each associated to one of the most characteristic chromosome changes. Cytogenetic characteristics and clinical aspects of the diseases are suggestive for the occurrence of two independent leukemic processes.