Interphase cytogenetic analysis in Argentinean B-cell chronic lymphocytic leukemia patients: association of trisomy 12 and del(13q14)

We have evaluated genomic aberrations by conventional cytogenetics and fluorescence in situ hybridization (FISH) analysis in a series of 57 Argentinean B-cell chronic lymphocytic leukemia (B-CLL) patients. The studies were performed on stimulated peripheral blood lymphocytes. FISH analysis for trisomy 12, 13q14 deletion, and monosomy of TP53 (also known as p53) was performed according to standard protocols. Our results showed 46.3% of patients with clonal chromosomal alterations by conventional cytogenetics and 80.7% by FISH. Trisomy 12 was found in 21.9% of patients by G-banding analysis and in 35% by FISH studies. Allelic loss of 13q14 was observed in 63.2% patients, most of them showing D13S319 and D13S25 deletion; 11% of patients showed TP53 monosomy. Coexistence of trisomy 12 and 13q14 deletion was found in 17.5% of patients. In this group, deletion 13q14 was the prevalent clone, with percentages 25-35% higher than those observed for trisomy 12, suggesting clonal evolution. The coexistence of trisomy 12 with deletion 13q14 was observed in a higher frequency than reported in the literature. A probable adverse prognosis is suggested for this group of patients, likely related to clonal evolution.     

Metaphase cells with normal G-bands have cryptic interstitial deletions in 13q14 detectable by fluorescence in situ hybridization in B-cell chronic lymphocytic leukemia

Interphase fluorescence in situ hybridization (FISH) studies with D13S319 show that deletions of 13q14 are common in B-cell chronic lymphocytic leukemia (B-CLL). In contrast, conventional cytogenetic studies in B-CLL seldom reveal abnormalities of chromosome 13. We hypothesized that chromosome 13 anomalies might not be detected because they are caused by cryptic deletions rather than by the absence of dividing B-CLL cells. To investigate this possibility, we used FISH with D13S319 to study metaphases from 12 patients known to have 13q- by interphase FISH. These same patients had normal chromosomes by conventional cytogenetic studies. As a result of this study, we report evidence that B-CLL metaphases with 13q- are not detected because these deletions are often cryptic and not visible by standard G-banding.     

Identification of 13q deletion, trisomy 1q, and IgH rearrangement as the most frequent chromosomal changes found in Korean patients with multiple myeloma

The most frequent genetic aberrations in multiple myeloma (MM) are 13q deletions and translocations involving the immunoglobulin heavy chain gene (IGH). There have been no reports on the cytogenetic abnormalities found in Korean patients with MM. We investigated the actual prevalence and prognostic value of cytogenetic changes using fluorescence in situ hybridization (FISH). FISH studies with 12 different specific probes for the regions containing the genes or chromosome regions (13q, 1q, IGH, p53, MLL, p16, CEP 7, CEP 11, and CEP 12) were performed in 128 patients. The most frequent change found was 13q deletion (48%), followed by trisomy 1q (45%), IGH translocation (37%), and trisomy 11 (26%). Among the three different probes used to detect 13q deletion, D13S25 (48/58) was the most sensitive probe compared to RB (43/58) and D13S319 (39/58). Among the patients showing one or more changes by FISH, 75% (82/110) had a 13q deletion, a trisomy 1q, or an IGH translocation. Azotemia, anemia, thrombocytopenia, intramedullary plasmacytosis, and stage were significantly associated with the 13q deletion; serum beta(2)-microglobulin, thrombocytopenia, and intramedullary plasmacytosis were also related to trisomy 1q. The pattern of molecular cytogenetic changes in Korean patients with MM is somewhat different from what has been observed in reported Caucasian populations: 37 versus 50-70% with regard to the IGH translocation. The prevalence of the 13q deletion was similar in Korean and Caucasian populations, 48 versus 30-50%. We suggest that the detection of at least these three genetic changes, 13q- trisomy 1q, and an IGH rearrangement, would be helpful for follow-up of Korean patients with MM.     

Multicolor FISH in chronic lymphocytic leukemia. An interphase study of patients with early-onset disease

Trisomy 12 and deletions of 13q14.2 and 14q32 are the most common chromosome abnormalities in patients with B-chronic lymphocytic leukemia (B-CLL), but whether specific chromosomal defects influence the course of B-CLL is still a matter of discussion. The aim of our study was to assess the possible correlation between cytogenetic findings and clinical characteristics. Thirty patients with previously untreated early-onset B-CLL were recruited. The incidence of trisomy 12, and observations of 13q14.2 and 14q32 was analyzed in unstimulated bone marrow cells by means of multicolor interphase FISH. No correlation was found between trisomy 12 and the patients' clinical characteristics. The analysis of the patients with trisomy 12 and observations of 13q14.2 and 14q32 revealed heterogeneity of the leukemic cell population, thus indicating that these chromosomal abnormalities are probably a secondary event in CLL leukemogenesis. The finding of RB1 gene nullisomy and 14q32 deletions in patients at an advanced clinical stage suggests a possible correlation between these rearrangements and disease progression. Multicolor FISH analysis in B-CLL provides important diagnostic, clinical, and prognostic information that may help in assessing prognosis and making treatment decisions.     

联合间期和中期荧光原位杂交检测发现11q23异常伴D13S319缺失急性髓系白血病一例

目的对1例出现11q23异常伴D13S319缺失的罕见急性髓系白血病(acute myeloid leukemia,AML)患者进行多途径细胞遗传学分析,为诊断、治疗及预后分层提供依据。方法应用G+R显带技术对患者24 h培养后的中期分裂相进行染色体核型分析,联合分裂间期和中期荧光原位杂交(fluorescence in situ hybridization,FISH)技术对患者染色体的特定位点进行检测,明确复杂易位和微小缺失片段。结果患者存在混合系白血病基因(mixed lineage leukemia,MLL)重排,形成了MLL-AF10融合基因,并伴有13号染色体D13S319位点的缺失。结论MLL基因重排合并D13S319位点缺失在急性白血病中是否具有双重打击效应应引起临床的重视。在AML患者核型中发现13q-、del(13)(q14)、-13或der(13)任意一种克隆性异常时,应行FISH检测论证及明确缺失片段的大小,以便进行靶向治疗。     

A der(13)t(7;13)(p13;q14) with monoallelic loss of RB1 and D13S319 in myelodysplastic syndrome

Deletions or translocations of chromosome band 13q14, the locus of the retinoblastoma gene (RB1), have been observed in a variety of hematological malignancies including myelodysplastic syndrome (MDS). We describe here a novel unbalanced translocation der(13)t(7;13)(p13;q14) involving 13q14 in a patient with MDS. A 66-year-old woman was diagnosed as having MDS, refractory anemia with excess of blasts (RAEB-1) because of 7.4% blasts and trilineage dysplasia in the bone marrow cells. G-banding and spectral karyotyping analyses showed complex karyotypes as follows: 46,XX,der(6)t(6;7)(q11;?),der(7)del(7)(?p13)t(6;7)(q?;q11)t(6;13)(q?;q?),der(13)t(7;13)(p13;q14). Fluorescence in situ hybridization (FISH) analyses demonstrated that one allele of the RB1 gene and the microsatellite locus D13S319, located at 13q14 and telomeric to the RB1 gene, was deleted. Considering other reported cases, our results indicate that submicroscopic deletions accompanying 13q14 translocations are recurrent cytogenetic aberrations in MDS. The RB1 gene or another tumor suppressor gene in the vicinity of D13S319, or both, may be involved in the pathogenesis of MDS with 13q14 translocations by monoallelic deletion.     

13q deletions in B-cell lymphoproliferative disorders: frequent association with translocation

The 13q14 deletion is the most frequent abnormality in chronic lymphocytic leukemias/small lymphocytic lymphomas, and this early rearrangement is observed from the start of the disease. The systematic use of a panel of interphase fluorescence in situ hybridization (FISH) may not reveal some probes (targeting chromosomes 11q, 13q, 17p, and chromosome 12) structural abnormalities. In this series, we analyzed metaphases by conventional cytogenetics, followed by interphase and metaphase fluorescence in situ hybridization. We were able to observe 17 cases of 13q translocations with deletions in eight of them. Three distinct regions were involved by translocations in association with or without deletions: a region centromeric to RB1 (13q11 approximately 13), a zone telomeric to D13D25 (13q21 approximately 31), and a 13q14 region deliniated by RB1 and D13S25. In this area, the deletion was variable: RB1 alone (one case), D13S319 approximately D13S25 (five cases), and from RB1 to D13S25 (two cases). The very high frequency of 13q14 loss suggests that these deletions are of pathogenetic importance, but, the importance of the translocations remains to be determined.     

A biological role for deletions in chromosomal band 13q14 in mantle cell and peripheral t-cell lymphomas?

Structural aberrations of chromosomal band 13q14 are frequent in B-cell chronic lymphocytic leukemia (B-CLL) and target a putative tumor suppressor gene in the genomic region between the RB1 gene and the genetic marker D13S25. Recently, it has been suggested that alterations of this particular region might also be of relevance for the pathogenesis of mantle cell lymphomas (MCL). We applied dual-color fluorescence in situ hybridization (FISH) using probes for the RB1 and/or D13S25 loci and screened a total of 236 B- and T-cell non-Hodgkin's lymphomas (NHL) for deletions occurring in this genomic region. In MCL, the high rate (12/32; 38%) of hemizygous deletions and especially a deletion pattern similar to B-CLL in four of the cases provide further evidence that a substantial proportion of MCL cases may share a common way of pathogenesis with B-CLL. In other B-cell NHL, the frequency of allelic loss affecting 13q14 was overall low. However, the finding of 13q14 microdeletions in seven cases without detectable alterations of chromosome 13 at G-banding analysis might indicate a possible involvement of this genetic region also for the lymphomagenesis of single cases of B-cell NHL other than B-CLL and MCL. In T-cell NHL, allelic loss at 13q14 was encountered in three of 13 peripheral T-NHL, NOS. Taking into account the very limited cytogenetic data yet available in this entity, our series provides further evidence that 13q14 changes might represent one of the most frequent genetic abnormalities in T-cell NHL.     

13q14 deletion size and number of deleted cells both influence prognosis in chronic lymphocytic leukemia

Deletion at 13q14 is detected by fluorescence in situ hybridization (FISH) in about 50% of chronic lymphocytic leukemia (CLL). Although CLL with 13q deletion as the sole cytogenetic abnormality (del13q-only) usually have good prognosis, more aggressive clinical courses are documented for del13q-only CLL carrying higher percentages of 13q deleted nuclei. Moreover, deletion at 13q of different sizes have been described, whose prognostic significance is still unknown. In a multi-institutional cohort of 342 del13q-only cases and in a consecutive unselected cohort of 265 CLL, we investigated the prognostic significance of 13q deletion, using the 13q FISH probes locus-specific identifier (LSI)-D13S319 and LSI-RB1 that detect the DLEU2/MIR15A/MIR16-1 and RB1 loci, respectively. Results indicated that both percentage of deleted nuclei and presence of larger deletions involving the RB1 locus cooperated to refine the prognosis of del13q-only cases. In particular, CLL carrying <70% of 13q deleted nuclei with deletions not comprising the RB1 locus were characterized by particularly long time-to-treatment. Conversely, CLL with 13q deletion in <70% of nuclei but involving the RB1 locus, or CLL carrying 13q deletion in ≥70% of nuclei, with or without RB1 deletions, collectively experienced shorter time-to-treatment. A revised flowchart for the prognostic FISH assessment of del13q-only CLL, implying the usage of both 13q probes, is proposed.     

Influence of clone and deletion size on outcome in chronic lymphocytic leukemia patients with an isolated deletion 13q in a population‐based analysis in British Columbia,Canada

Deletion of the long arm of chromosome 13 (del(13q)) as the sole abnormality in chronic lymphocytic leukemia (CLL) portends a good prognosis; however, there is great outcome heterogeneity within this subgroup. The percentage of cells with a del(13q) (clone size) and the extent of the deletion are two factors that may affect outcome in CLL patients with isolated del(13q). We analyzed 248 CLL patients from the BC Provincial CLL database identified as having isolated del(13q) detected pretreatment by interphase fluorescence in situ hybridization to determine what impact clone and deletion size had on overall survival (OS) and treatment free survival (TFS). Patients with 60% or more of nuclei with a del(13q) had shorter TFS and shorter OS. A large deletion, encompassing the RB1 gene locus, was detected in half of the 90 cases with available specimens for testing, and there was no significant difference in OS and TFS between RB1‐deleted and RB1‐not‐deleted cases. Further study in a larger sample size is required to determine the clinical interest of RB1 locus testing; however, clone size of del(13q) does predict TFS and OS and may better refine prognosis in this clinically heterogeneous population. © 2015 Wiley Periodicals, Inc.     

Polysomy 13 with concomitant deletion of 13q13-14 involving the retinoblastoma gene and the D13S25 locus in a case of acute myeloid leukemia

We herein describe a case of acute myeloblastic leukemia (AML), FAB subtype M4, with an unfavorable clinical course and a complex karyotype, including 4-9 copies of chromosome 13. Polysomy 13 was a result of clonal evolution. Fluorescence in situ hybridization (FISH) revealed a cytogenetically unrecognizable deletion within 13q13-14 that included the retinoblastoma gene (RB) and the D13S25 locus in all but one copy of chromosome 13. The only chromosome 13 that did not show a deletion affecting the q13-14 region was translocated to chromosome 7, resulting in a dic(7;13)(q21;p11). In this case, the coexistence of polysomy and a partial deletion within the same chromosome point toward a possible formation of a fusion product with oncogenic potential and its consecutive amplification as a critical alteration in this case.     

Genetic abnormalities and clinical outcome in chronic lymphocytic leukemia

B-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in the elderly population. Under conventional cytogenetic (CC) analysis, approximately 50% of CLL cases show clonal aberrations. Using fluorescent in situ hybridization (FISH), the percentage of patients with abnormalities rises to almost 80%, the most frequent being 13q14, ATM, and TP53 deletions and trisomy 12. The aim of this study was to establish the incidence of genetic changes in B-CLL patients using CC and FISH and to evaluate the prognostic implications. Of the 65 patients analyzed, genetic aberrations were found in 36.7% with CC and in 68.4% with FISH. The frequencies of abnormalities were as follows: 13q deletion, 42.1%; trisomy 12, 19.2%; ATM deletion, 17.5%; and TP53 deletion, 8.7%. Significant differences were observed when the overall survival was correlated with Rai stage (P = 0.000). FISH abnormalities were correlated with age, sex, morphology, white blood cell count, CD38 expression, Rai stage, disease status, and survival. Significant differences were obtained with age (P = 0.05) and disease status (P = 0.01). Deletion of 13q was the most frequent abnormality (36.6%) among old patients (> or =60); trisomy 12 was the most frequent (31.3%) in younger patients (<60). Half of the patients with stable disease showed 13q deletion, and the most frequent abnormality in patients with progressive disease was ATM deletion (22.2%).     

Cytogenetics of agnogenic myeloid metaplasia: a study of 61 patients

Agnogenic myeloid metaplasia (AMM) or idiopathic myelofibrosis is a chronic myeloproliferative disorder characterized by fibrotic bone marrow, extramedullar haematopoiesis, and a leukoerythroblastic picture in circulating blood. The cytogenetic data on AMM are scanty and no recurring chromosome abnormality has been associated with the natural course of this disease. Trisomy 1q, del(13q), del(20q), and trisomy 8, appear in about two thirds of patients with demonstrable chromosome aberrations. We report on the cytogenetic analyses of 61 consecutive patients with AMM studied at diagnosis. The metaphases could not be found in 10/61 (16.4%) patients, and chromosome studies were successful in 51 patients. Twenty-one patients (41%) had an abnormal clone, whereas 30 (59%) patients had a normal karyotype. Most frequent pathological findings included trisomy 8 (either alone or within a complex karyotype) in five patients, aberrations of chromosome 12 (translocation in two, monosomy in two, and trisomy in one patient), and aberrations of chromosome 20 (interstitial deletion in two, monosomy in two, and trisomy in one patient). We also detected aberrations of chromosome 13 (translocation in two and an interstitial deletion and trisomy in one patient each) and chromosome 18 (derivative 18 in two patients and a monosomy and deletion in one patient each). Three patients exhibited complex aberrations involving several chromosomes, sometimes with a mosaicisam. A near-tetraploid karyotype was observed in a single patient. Balanced translocations [t(2;16)(q31;q24), t(5;13)(q13;q32), t(12;13)(p12;q13), and t(12;16)(q24;q24)] were present in four patients. While the series of patients studied displayed chromosomal aberrations that are frequently observed in AMM, we found some new abnormalities (balanced translocations and polyploidy) that are rarely observed in AMM.     

应用组合荧光原位杂交技术检测慢性淋巴细胞白血病的基因组异常

目的 探讨应用组合荧光原位杂交(panel fluorescence in situ hybridization，panel FISH)技术对慢性淋巴细胞性白血病(chronic lymphocytic leukaemia，CLL)基因组异常检测的价值。方法 分别应用3号、12号、18号的着丝粒探针和序列探针D13S272(13q14．3)、ATM(11q23)等5种荧光素标记的DNA探针，对22例CLL患者进行FISH检测，并和常规细胞遗传学检测结果进行比较，以确定何种方法对检测CLL的染色体和基因组异常更为敏感可靠。结果 22例CLL患者中，常规细胞遗传学检测出8例(36．3％)有染色体异常，包括单纯 123例； 3、 12l例； 3、 12、 18 1例；t(5；15)1例；13q-1例；3q-、18p 1例；4q 和13q-1例；组合FISH检测出15例(68，1％)有染色体异常，包括 34例、 126例、 18l例、11q-6例、13q-8例。结论组合。FISH技术是检测CLL患者染色体基因组异常的有效手段，与常规细胞遗传学方法相结合则可明显提高CLL染色体异常的检出率。     

荧光原位杂交技术检测多发性骨髓瘤复杂核型异常

目的探讨多重荧光原位杂交(multiplex fluorescence in situ hybridization,M-FISH)技术联合荧光原位杂交(fluorescence in situ hybridization,FISH)技术在检测多发性骨髓瘤(multiplemyeloma,MM)染色体异常中的应用价值及13q14缺失、IgH相关易位和17p13缺失的发生率。方法联合应用常规细胞遗传学(conventional cytogenetics,CC)方法及M-FISH和一组包括13q14(D13S319),14q32(IgH基因)和17p13(p53基因)探针的FISH技术分析了7例伴有复杂染色体异常的MM患者骨髓标本。结果M-FISH明确了CC分析中没有明确的异常,共检出12种染色体数目异常和29种结构异常,其中,1号染色体异常、13号染色体缺失和与14q32相关的易位最为多见。FISH检出6例伴有13q14缺失;4例伴有17p13缺失;5例伴有一个14q32相关易位,两例还伴有涉及两个14q32的易位。结论M-FISH联合FISH技术可以明确CC分析中复杂染色体异常,并发现和纠正CC分析中漏检及误检的异常,为MM染色体异常的研究提供了一种理想的     

t(15;21)(q15;q22.1)pat resulting in partial trisomy and partial monosomy of chromosomes 15 and 21 in two offspring

Two sibs, carriers of unbalanced products of the translocation t(15;21)(q15;q22.1)pat, are described. The sister had Prader-Willi syndrome due to deletion 15 (pter > q15) and partial trisomy 21 (pter > q22.1); her brother had partial trisomy 15 (pter > q15) and partial monosomy 21 (pter > q22.1). The translocation breakpoint on chromosome 21 was located proximal to the SOD1 gene, within a region of 4.0 cM (2.3 Mb) between the loci D21S217 and D21S213. The correlations between the clinical presentation and the molecular findings of the two sibs are discussed in relation to other patients with partial trisomy and monosomy 21. © 1996 Wiley-Liss, Inc.     

Interstitial 13q14 deletions detected in the karyotype and translocations with concomitant deletion at 13q14 in chronic lymphocytic leukemia: Different genetic mechanisms but equivalent poorer clinical outcome

Deletion of 13q14 as the sole abnormality is a good prognostic marker in chronic lymphocytic leukemia (CLL). Nonetheless, the prognostic value of reciprocal 13q14 translocations [t(13q)] with related 13q losses has not been fully elucidated. We described clinical and biological characteristics of 25 CLL patients with t(13q), and compared with 62 patients carrying interstitial del(13q) by conventional G‐banding cytogenetics (CGC) [i‐del(13q)] and 295 patients with del(13q) only detected by fluorescence in situ hybridization (FISH) [F‐del(13q)]. Besides from the CLL FISH panel (D13S319, CEP12, ATM, TP53), we studied RB1 deletions in all t(13q) cases and a representative group of i‐del(13q) and F‐del(13q). We analyzed NOTCH1, SF3B1, and MYD88 mutations in t(13q) cases by Sanger sequencing. In all, 25 distinct t(13q) were described. All these cases showed D13S319 deletion while 32% also lost RB1. The median percentage of 13q‐deleted nuclei did not differ from i‐del(13q) patients (73% vs. 64%), but both were significantly higher than F‐del(13q) (52%, P < 0.001). Moreover, t(13q) patients showed an increased incidence of biallelic del(13q) (52% vs. 11.3% and 14.9%, P < 0.001) and higher rates of concomitant 17p deletion (37.5% vs. 8.6% and 7.2%, P < 0.001). RB1 involvement was significantly higher in the i‐del(13q) group (79%, P < 0.001). Two t(13q) patients (11.8%) carried NOTCH1 mutations. Time to first treatment in t(13q) and i‐del(13q) was shorter than F‐del(13q) (67, 44, and 137 months, P = 0.029), and preserved significance in the multivariate analysis. In conclusion, t(13q) and del(13q) patients detected by CGC constitute a subgroup within the 13q‐deleted CLL patients associated with a worse clinical outcome. © 2014 Wiley Periodicals, Inc.     

Retinoblastoma gene deletions in B-cell chronic lymphocytic leukemia.

Approximately 10% of B-cell chronic lymphocyte leukemia (B-CLL) cases have structural chromosomal aberrations involving band 13q14. To evaluate a possible role of RBl gene deletions in B-CLL we investigated the malignant cells of 27 patients by molecular genetic and cytogenetic techniques. Four of the cases had chromosomal aberrations that involved 13q14 (including one case with a 13q14 deletion that was observed in a single metaphase cell), and 11 had other chromosomal abnormalities, whereas the malignant cells of 12 patients were either cytogenetically normal or failed to divided in vitro. Eight patients (30%) were found to have hemizygous deletions of the RBl gene. These cases included all four patients with chromosomal changes at 13q14, but also three patients without chromosome abnormalities and one case with a chromosomal aberration not involving 13q. The deletions were interstitial in all cases but one, as defined by probes located centromeric and telomeric of the RBl locus. Inactivation of RBl may thus be a significant event in the development of some B-CLL clones.     

Chromosome analyses in chronic lymphocytic leukemia and related B-cell neoplasms

Chromosome analyses were performed by routine G-banding in 29 patients with B-cell chronic lymphocytic leukemia (B-CLL), six with immunocytoma (IC), three with centroblastic-centrocytic (cb-cc) lymphoma, and one with hairy cell leukemia (HCL). Ages of the patients were between 46 and 81 years (mean, 63 years). 12-O-tetradecanoyl-phorbol-13-acetate (TPA) was used as a mitogen to stimulate leukemic B-cells in 72-hour cultures. Twenty-one patients had one or more chromosomal abnormalities; and in 13 patients, they were clonal; 18 patients had a normal karyotype. Seven patients had trisomy 12 (three B-CLL, two IC, two cb-cc lymphoma); two (B-CLL) had it as the sole abnormality. One patient with B-CLL had trisomy 18 as the sole abnormality, and one with IC had trisomy 18 in combination with trisomy 19. One patient with B-CLL had t(1;6)(p36;p21) as a clonal structural abnormality. A t(11;14)(q13;q32) was consistently observed in one patient with cb-cc lymphoma together with inv(1) (p22p36), der(4)t(4;?)(p16;?), del(6)(q13) and other variable changes. One patient with morphologically atypical B-CLL had t(1;11)(p36;q13) together with der(X)t(X;?)(q26;?), der(3)t(3;?)(q29;?), der(8)t(4;8)(q12;q24.1) and additional variable changes. Both patients with these complex karyotypes were in an advanced stage of disease (Binet stage C) and died within 3-6 months after chromosome analysis.     

Aberrations in chromosomes associated with lymphoma and therapy-related leukemia in benzene-exposed workers

Epidemiological studies show that benzene exposure is associated with an increased incidence of leukemia and perhaps lymphoma. Chromosomal rearrangements are common in these hematopoietic diseases. Translocation t(14;18), the long-arm deletion of chromosome 6 [del(6q)], and trisomy 12 are frequently observed in lymphoma patients. Rearrangements of the MLL gene located on chromosome 11q23, such as t(4;11) and t(6;11), are common in therapy-related leukemias resulting from treatment with topoisomerase II inhibiting drugs. To examine numerical and structural changes in these chromosomes (2, 4, 6, 11, 12, 14, and 18), fluorescence in situ hybridization (FISH) was employed on metaphase spreads from workers exposed to benzene (n = 43) and matched controls (n = 44) from Shanghai, China. Aneuploidy (both monosomy and trisomy) of all seven chromosomes was increased by benzene exposure. Benzene also induced del(6q) in a dose-dependent manner (P(trend) = 0.0002). Interestingly, translocations between chromosomes 14 and 18, t(14;18), known to be associated with follicular non-Hodgkin lymphoma, were increased in the highly exposed workers (P < 0.001). On the other hand, translocations between chromosome 11 and other partner chromosomes that are found in therapy-induced leukemias were not increased. These data add weight to the notion that benzene can induce t(14;18) and del(6q) found in lymphoma, but do not support the idea that benzene induces t(4;11) or t(6;11). However, they do not rule out the possibility that other rearrangements of the MLL gene at chromosome 11q23 may be induced by benzene.