Specific Chromosomal Abnormalities Research Articles

Variation in RNA expression and genomic DNA content acquired during cell culture.

Specific chromosomal abnormalities are increasingly recognised to be associated with particular tumour subtypes. These cytogenetic abnormalities define the sites of specific genes, the alteration of which is implicated in the neoplastic process. We used comparative genomic hybridisation (CGH) to examine DNA from different breast and ovarian cancer cell lines for variations in DNA sequence copy number compared with the same normal control. We also compared different sources of the MCF7 breast line by both CGH and cDNA expression arrays. Some of the differences between the subcultures were extensive and involved large regions of the chromosome. Differences between the four subcultures were observed for gains of 2q, 5p, 5q, 6q, 7p, 7q, 9q, 10p, 11q, 13q, 14q, 16q, 18p and 20p, and losses of 4q, 5p, 5q, 6q, 7q, 8p, 11p, 11q, 12q, 13q, 15q, 19p, 19q, 20p, 21q, 22q and Xp. However, few variations were found between two subcultures examined, 5 months apart, from the same initial source. The RNA arrays also demonstrated considerable variation between the three different subcultures, with only 43% of genes expressed at the same levels in all three. Moreover, the patterns of the expressed genes did not always reflect our observed CGH aberrations. These results demonstrate extensive genomic instability and variation in RNA expression during subculture and provide supportive data for evidence that cell lines do evolve in culture, thereby weakening the direct relevance of such cultures as models of human cancer. This work also reinforces the concern that comparisons of published analyses of cultures of the same name may be dangerous.

Molecular cytogenetics in childhood leukemia.

In the last decade molecular cytogenetics, or fluorescence in situ hybridization (FISH), has become an important complementary procedure to routine chromosomal analysis. The most significant consequence from cytogenetic studies in childhood leukemia has been the association of specific chromosomal abnormalities with different patient subgroups, particularly in relation to prognosis. In childhood acute myeloid leukemia (AML), the rearrangements t(8;21)(q22;q22), t(15;17)(q22;q12), and inv(16)(p13q22) are associated with a good outcome. Conversely, deletions of the long arm of chromosome 5, monosomy 5 or 7, in association with a complex karyotype, are related to a poor prognosis. Karyotypes with a favorable outcome in childhood acute lymphoblastic leukemia (ALL) include high hyperdiploidy (51-65 chromosomes) and the translocation, t(12;21)(p13;q22). The Philadelphia translocation, t(9;22)(q34;q11), rearrangements involving the MLL gene and near haploidy (23-29 chromosomes) are associated with a short overall survival (2). Metaphase and interphase FISH are increasingly being used to screen routinely for such chromosomal abnormalities in childhood leukemia. Metaphase FISH also plays a role in the identification of new nonrandom chromosomal changes of prognostic significance.

API2-MALT1 Fusion Gene in Colorectal Lymphoma

The API2-MALT1 fusion gene was originally identified from a t(11;18)(q21;q21) translocation, a specific chromosomal abnormality that is found in mucosa-associated lymphoid tissue (MALT) lymphoma. Gastric MALT lymphomas positive for the API2-MALT1 fusion gene do not respond to Helicobacter pylori–eradication therapy, but otherwise, the incidence and clinicopathological behavior of colorectal MALT lymphoma with this genetic abnormality are unclear. We examined the API2-MALT1 fusion by multiplex RT-PCR method in 47 cases of MALT lymphoma and 13 cases of diffuse large B-cell lymphoma and evaluated the relevance of API2-MALT1 positivity to the clinical and pathological features. The mean ages of MALT lymphoma and diffuse large B-cell lymphoma patients were 65 (range, 37–87 y) and 58 (range, 14–85 y) years, respectively. API2-MALT1 fusion genes were detected in seven cases (15%) of MALT lymphoma and one case (8%) of diffuse large B-cell lymphoma. In MALT lymphomas, the tumor size in API2-MALT1–positive cases was 62 ± 39 mm (mean ± SD), statistically larger than that in API2-MALT1–negative cases (25 ± 19 mm; P < .01). The API2-MALT1–positive cases demonstrated more advanced clinical stages and a male predominance, compared with API2-MALT1–negative cases. Thus, API2-MALT1–positive tumors should be cared for as a more aggressive subgroup and be followed for a longer time.

New cytokine-dependent acute myeloid leukemia cell line MUTZ-11 with disomic chromosome rearrangement t(16;17)

Continuous human leukemia–lymphoma (LL) cell lines represent a rich resource of abundant, accessible and manipulable living cells contributing significantly to a better understanding of the pathophysiology of hematopoietic tumors. In particular, classical and molecular cytogenetics have benefitted enormously from the availability of LL cell lines with specific chromosomal abnormalities. Such aberrations may be the portal to the discovery of novel oncogene rearrangements for which positive cell lines provide a resource for both discovery and functional studies. The new continuous leukemia cell line MUTZ-11 was established in 1994 from the peripheral blood of a 60-year-old woman with acute myeloid leukemia (AML) M4 (following 2 years with myelodysplastic syndromes). DNA fingerprinting confirmed the authenticity and derivation of the cell line. The immunoprofile as determined by flow cytometry was as follows: positive for myelocytic markers (CD13, CD15, CD33, CD65 and CD68), negative for T-cell (except for CD4 and CD7), B-cell and erythroid-megakaryocytic markers. The cell line is constitutively cytokine-dependent and growth depends on externally added cytokines. With regard to cytokine receptor expression, the cell line was found to be positive for GM-CSFRα (granulocyte-macrophage colony-stimulating factor receptor, CD116), Kit (CD117) and IL-3Rα (interleukin-3 receptor, CD123). The cytokine response profiles as determined by [ 3 H ]-thymidine incorporation assay were: 2-to-12 fold growth stimulation of MUTZ-11 by GM-CSF, IFN-α (interferon), IFN-β, IFN-γ, IL-3 and SCF (stem cell factor); growth inhibition by TGF-β1 (transforming growth factor), TNF-α (tumor necrosis factor) and TNF-β. Cytogenetic analysis showed the following consensus karyotype: 46, XX, der(16)t(16;17)(p13.3;q23)x2. Previous molecular biological analysis documented that MUTZ-11 cells carry both an FLT3 internal tandem duplication (ITD) and an MLL partial tandem duplication (PTD). The scientific significance of MUTZ-11 lies (i) in the absolute cytokine-dependency and the proliferative response to various cytokines, (ii) in the unique cytogenetic (disomic t(16;17)) and (iii) molecular biological alterations ( FLT3 ITD + MLL PTD). In summary, the new cytokine-dependent AML-derived cell line MUTZ-11 displays unique novel features and emphasizes the need for comprehensive analysis of new LL cell lines which may lead to the discovery of important pathogenetic alterations.

Imatinib mesylate inhibits autonomous erythropoiesis in patients with polycythemia vera in vitro

AbstractThe overproduction of red blood cells in patients with polycythemia vera (PV) is reflected in vitro by the formation of erythroid burst-forming units (BFU-Es) in the absence of exogenous erythropoietin. In contrast to other myeloproliferative disorders, the molecular mechanism of PV is unknown and no specific chromosomal abnormality has been described. We speculated that imatinib mesylate may reverse the pathological overproduction of red cells by inhibition of autonomous erythropoiesis. In the present study, imatinib mesylate was found to either block or strongly inhibit autonomous BFU-E formation in vitro in all patients tested. Moreover, autonomous BFU-E growth was also markedly reduced by exposure of PV cells to imatinib mesylate prior to cultivation in semisolid medium. The profound effect of imatinib mesylate on autonomous erythropoiesis suggests the involvement of an as yet unidentified kinase in the pathogenesis of PV and should provide the rationale for a forthcoming clinical trial.

Is reduced blastocyst development associated with chromosomal abnormality after PGD?

Objective: Preimplantation genetic diagnosis (PGD) procedures are commonly used to check for specific genetic diseases and chromosomal abnormalities. This study was undertaken to determine if preembryo morphology on day 3 and rate of blastocyst development on day 5 are associated with PGD results.

Hamartomas of the lung

mained stable in size, while the other 50% grew at a rate of approximately 3 mm per year. These lesions, while generally peripheral or subpleural in location, are distributed evenly throughout all lobes of the lung. A subset of hamartomas, endobronchial hamartomas, account for 1% to 20% of lesions and are more likely to cause signs or symptoms such as dyspnea, wheezing, or recurrent infections due to airway obstruction. 5,6 Endobronchial hamartomas are particularly interesting because cytogenetics studies have shown specific chromosomal abnormalities that suggest a clonal origin of these lesions. 7

Prevalence and clinical characteristics of myelodysplastic syndrome with bone marrow eosinophilia or basophilia

By retrospectively analyzing 288 patients with de novo myelodysplastic syndrome (MDS), we sought to determine the prevalence and clinical characteristics of bone marrow eosinophilia and basophilia that were detected at presentation. Bone marrow eosinophilia and basophilia were defined as a differential count of each cell type exceeding 5.0% and 1.0%, respectively. Of 288 patients with MDS, 36 (12.5%) fulfilled this criterion for bone marrow eosinophilia (MDS-Eos); 34 patients (11.8%) showed basophilia (MDS-Bas), and 11 (3.8%) satisfied both criteria (MDS-EosBas). The remaining 229 patients had neither eosinophilia nor basophilia in their bone marrow (MDS(-/-)) at presentation. Cytogenetic analysis was carried out on unstimulated bone marrow cells obtained from 264 patients. When the cytogenetic categorization of the IPSS (International Prognostic Scoring System) for MDS was applied, significantly higher numbers of MDS-Eos and MDS-Bas patients had chromosomal abnormalities carrying intermediate or poor prognosis, compared with the MDS(-/-) patients. Specific chromosomal abnormalities and complex karyotypes were associated with MDS-Eos and/or MDS-Bas. In accordance with these results, the overall survival rate was significantly lower, and the evolution to acute myelogenous leukemia (AML) occurred more frequently in the MDS-Eos and MDS-Bas than in the MDS(-/-) patients. Multivariate analysis demonstrated that bone marrow basophilia was an independent risk factor for evolution to AML. Our study indicates that bone marrow eosinophilia and basophilia in patients with MDS predict a poorer prognosis.

Assessment of the Effectiveness of Genetic Counseling by Telephone Compared to a Clinic Visit.

Maternal serum screening, also known as the triple screen, is used during pregnancy to assess the risk of carrying a fetus with specific chromosome abnormalities or open spina bifida. All women in British Columbia who screen positive are eligible for genetic counseling and are offered amniocentesis. The purpose of this study is to determine what differences (if any) exist in patients' understanding and/or anxiety when genetic counseling for a positive triple screen is conducted in person versus over the telephone. Each patient who participated was given the choice of having genetic counseling in person or over the telephone, this after a randomized design failed to elicit any participants. Using a written postcounseling questionnaire, each patient was assessed for her understanding of the information presented in the session, and her anxiety regarding her risk. In this small pilot study, no large differences were detected in patients' understanding or anxiety when genetic counseling was conducted by telephone versus in person.

The eosinophilias, including the idiopathic hypereosinophilic syndrome.

The eosinophilias, including the idiopathic hypereosinophilic syndrome.

Chromosome abnormalities clustering and its implications for pathogenesis and prognosis in myeloma.

The nonrandom recurrent nature of chromosome abnormalities in myeloma suggests a role for them in disease pathogenesis. We performed a careful cytogenetic analysis of patients with abnormal karyotypes (n = 254), to discern patterns of association, search for novel abnormalities and elucidate clinical implications. Patients with karyotypic abnormalities suggestive of myelodysplasia/acute leukemia were excluded. In this study we compared survival by abnormality only between patients with abnormal karyotypes. Patients with abnormalities were more likely to have features of aggressive disease as compared to all other patients without abnormalities entered into the myeloma database (lower hemoglobin, higher beta(2)-microglobulin, labeling-index and plasmocytosis; all P < 0.0001). Several groups of patients could be readily identified; hypodiploid (22%), pseudodiploid (36%), hyperdiploid (31%) and near-tetraploid (11%). Clustering associations were seen among several trisomies and monosomy of chromosome 13 and 14. Several monosomies (-2, -3, -13, -14 and -19), 1p translocations/ deletions, and hypodiploidy were associated with a significantly shorter survival. Trisomy of chromosome 13 was rare ( <2%). Even among patients with abnormal karyotypes, specific chromosome abnormalities can impart biologic variability in myeloma, including several monosomies, hypodiploidy and abnormalities of 1p.

Detection of a novel reciprocal t(16;22)(q11.2;q12) in a Ewing sarcoma

Several structural and numerical chromosomal abnormalities have been identified as primary and secondary chromosomal aberrations in Ewing sarcoma (ES). The majority of these are t(11;22) and trisomies, especially of chromosome 8. Specific chromosomal abnormalities often correlate with particular morphologic or phenotypic subtypes of tumor and play an important role in prognosis. The objective of this report is the cytogenetic evaluation of a case of ES using G-banding, fluorescence in situ hybridization, and spectral karyotyping techniques. Multiple chromosomal aberrations were identified including a novel reciprocal t(16;22)(q11.2;q12).

Delineation of an estimated 6.7 MB candidate interval for an anophthalmia gene at 3q26.33-q28 and description of the syndrome associated with visible chromosome deletions of this region.

Anophthalmia or microphthalmia occur in approximately one in 10 children who have severe visual impairment. These eye malformations are often of unknown aetiology, but can be inherited in autosomal dominant, recessive or X-linked forms, and can also occur in association with specific chromosome abnormalities. Four children are described in the medical literature with microphthalmia or anophthalmia in association with chromosome rearrangements involving distal 3q, suggesting the presence of a micro/anophthalmia gene in this region. We have identified two further patients with micro/anophthalmia and chromosome rearrangements involving 3q26-->3q27 and identified a 6.7 MB common deleted region. Patient 1 had multiple abnormalities including bilateral anophthalmia, abnormalities of the first and second cranial nerves and partial absence of the corpus callosum. His karyotype was 46,XY,del(3)(q26.33q28). Patient 2 had right anophthalmia and left extreme microphthalmia. Her karyotype was 46,XX,del(3)(q26.33q28)t(3;7)(q28;q21.1). Both patients had intrauterine growth retardation (IUGR) and strikingly similar dysmorphic facies consisting of bossed forehead, downward-slanting palpebral fissures, grooved bridge of the nose, prominent low-set ears, small down-turned mouth and small mandible. We identified BAC clones mapping to distal 3q from the ENSEMBL and NCBI Entrez databases. These BAC clones were used as fluorescence in situ hybridisation (FISH) probes to identify the minimum deleted region common to both patients. This interval, between clones RPC11-134F2 and RPC11-132N15, was estimated to be 6.7 MB. We conclude that there is an anophthalmia locus within this interval. Candidate genes mapping to this region include Chordin and DVL3, a homologue of the Drosophila Dishevelled gene.

Animal in vivo models of EBV-associated lymphoproliferative diseases: special references to rabbit models.

Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-associated diseases. Here we review those previous models using EBV or EBV-like herpesviruses and describe the details on our two newly-developed rabbit models of lymphoproliferative diseases (LPD) induced by simian EBV-like viruses. The first is Cynomolgus-EBV-induced T-cell lymphomas in rabbits inoculated intravenously (77-90%) and orally (82-89%) during 2-5 months. EBV-DNA was detected in peripheral blood by PCR from 2 days after oral inoculation, while anti-EBV-VCA IgG was raised 3 weeks later. Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphoma cell lines, most of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The second is the first animal model for EBV-infected T-cell LPD with virus-associated hemophagocytic syndrome (VAHS), using rabbits infected with an EBV-like herpesvirus, Herpesvirus papio (HVP). Rabbits inoculated intravenously with HVP-producing cells showed increased anti-EBV-VCA-IgG titers, and most (85%) subsequently died of fatal LPD and VAHS, with bleeding and hepatosplenomegaly, during 22-105 days. Peroral spray of cell-free HVP induced viral infection with seroconversion in 3 out of 5 rabbits, with 2 of the 3 infected rabbits dying of LPD with VAHS. Atypical T lymphocytes containing HVP-DNA and expressing EBER-1 were observed in many organs. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. These rabbit models are also useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens.

Cytogenetics in acute myeloid leukemia.

Cytogenetic analysis is the most important diagnostic tool for determining prognosis in acute myeloid leukemia (AML). In the majority of patients with AML, acquired clonal chromosome aberrations can be observed. Numerous recurrent karyotype abnormalities have been discovered in AML. These findings on the chromosomal level have paved the way for molecular studies that have identified genes involved in the process of leukemogenesis. The identification of specific chromosomal abnormalities and their correlation with cytomorphologic features, immunophenotype, and clinical outcome have led to a new understanding of AML as a heterogeneous group of distinct biologic entities. The importance of cytogenetic findings in AML for classification and for the understanding of pathogenetic mechanisms is increasingly appreciated in the clinical context, and the new World Health Organization classification of AML uses cytogenetic abnormalities as a major criterion.

Chromosomal Alterations in Hepatocellular Carcinoma Cell Lines Detected by Comparative Genomic Hybridization.

There have only been a few cytogenetic studies of hepatocellular carcinoma (HCC), and so far, no consistent specific chromosomal abnormalities have been described. Here, we have used comparative genomic hybridization (CGH), a powerful molecular cytogenetic technique for detecting changes of the copy number throughout the genome, to screen for genetic alterations in HCC cell lines. The CGH results were compared with those derived from G-banding and chromosome painting. MATERIALS AND METGODS: Conventional cytogenetic analyses were performed on five HCC cell lines, SNU-354, SNU-368, SNU-387, SNU-449 and SNU-475, using a G- banding staining technique. In CGH, equal amounts of differently labeled DNA from the cell lines, and normal reference DNA, were hybridized simultaneously to normal metaphase chromosomes. They were visualized by different fluorochromes, and the signal intensities quantified separately as gray levels along the single chromosomes. The over- and under-represented DNA segments were determined by computation of ratio images and average ratio profiles. To confirm the CGH results, florescence in situ hybridization (FISH), with chromosome specific painting, was performed using indirectly labeled chromosome specific paints. Complex unbalanced chromosomal aberrations, which could not be identified reliably by conventional cytogenetics in HCC cell lines, were successfully resolved by CGH analysis. CGH results were validated using FISH with chromosome specific probes. In HCC cell lines, gains in DNA copy number were more common than losses. The most prominent changes were gains of 1q12- qter (80% of cases), 1q41-qter (100%), 7 (80%), 8q12-qter (60%), 8q23-qter (80%) and 20q12-qter (60%). Recurrent losses were mapped on 4q13-qter (60%), 16q12-qter (60%), 16q21-qter (80%), 13q12-q14.2 (60%) and Yq11.2 (100%). All four male HCC cell lines showed loss or rearrangement of the Y chromosome. Conventional cytogenetics, CGH and FISH using painting probes, represent complementary approaches that, when employed in combination, could greatly facilitate the comprehensive analysis of chromosomal imbalances in HCC cell lines. Our results suggest the existence of an oncogene, or protooncogenes, on chromosome 1q41-qter, and the tumor suppressor genes on Yq11.2, that play a role in the development and/or progression of hepatocellular carcinogenesis.

Cytogenetic and histologic findings in Wilms' tumor

Purpose: The cytogenetic abnormalities occurring in Wilms' tumors diagnosed and treated at the authors' institution were reviewed. Correlation with tumor histopathology, stage, and outcome were evaluated. Methods: Sixty-seven Wilms' tumors were encountered between 1984 and 1997. Tissue culture was obtained in 63 (94%) cases. Charts were reviewed retrospectively to obtain tumor histopathology, stage, and outcome. Results: All tumors were examined in accordance with the National Wilms' Tumor Study (NWTS). Sixty-one were unilateral (54 unicentric, 7 multicentric), and 6 were bilateral (2 multicentric). Five Wilms' tumors showed anaplasia, whereas 62 showed favorable histology. Twenty children were stage I, 17 stage II, 20 stage III, 4 stage IV, and 6 stage V. Forty-eight (72%) tumors showed an abnormal karyotype. Chromosomal gain was more common than chromosomal loss, because hyperdiploidy was seen in 30 cases and hypodiploidy in 4. The most common aneuploidies were gains of chromosomes 6, 7, 8, 12, 13, and 18. In general, there was no correlation between specific chromosomal abnormalities with either tumor stage or histologic subtype. The only exceptions were anaplastic changes that were associated with poor prognosis and showed a variety of chromosomal changes including hyperdiploidy, hypodiploidy, and structural rearrangements. The 3 tumors causing mortality exhibited tetraploidy, hypodiploidy, and diploidy with a t(1p:11q) karyotype, respectively. Clonal progression was identified in Wilms' tumors when compared with its accompanying nephrogenic rest. A normal karyotype was seen more commonly in younger patients. Conclusions: Wilms' tumors display a variety of chromosomal abnormalities. These are particularly seen in anaplastic tumors and are less likely seen in younger patients. Overall, chromosomal gain was more common than loss with trisomies of chromosomes 12, 8, and 6 being the most frequently seen. J Pediatr Surg 37:823-827. Copyright 2002, Elsevier Science (USA). All rights reserved.

Adrenal myelolipoma with translocation (3;21)(q25;p11)

Adrenal myelolipoma (ML) is a rare, benign, nonfunctioning tumor-like lesion composed of mature adipose tissue interspersed with bone marrow-like hematopoietic elements in various proportions. It occurs usually in adults and is frequently asymptomatic in about half of cases. The histogenesis of adrenal ML is not clear and this lesion has been found to be associated with endocrine disorders, other adrenal dysfunction and tumors, and hyperstimulation with adrenocorticotropic hormone. Specific chromosomal abnormalities, however, have not been observed in such cases. Herein, we report a typical case of adrenal ML found incidentally in a 26-year-old man. Conventional cytogenetic techniques demonstrated balanced translocation between bands 3q25 and 21p11 in 9 of 20 metaphases analyzed in cultured tumor cells. To the best of our knowledge, this is the first reported case of adrenal ML showing chromosomal abnormality. This finding would indicate that adrenal ML is a bona fide neoplasm and the possibility of derivation from misplaced hematopoietic cells may be alternatively taken into consideration in view of the similar genetic changes in hematopolietic neoplasms.

Expression of PLAG1 and HMGIC proteins and fusion transcripts in radiation-associated pleomorphic adenomas

Extensive cytogenetic investigations of pleomorphic adenomas of the salivary glands have unequivocally demonstrated that they are cytogenetically monoclonal and are characterized by a high frequency of tumor specific chromosome abnormalities involving in particular chromosome bands 3p21, 8q12 and 12q14-15. Here we show that two radiation-associated and cytogenetically polyclonal adenomas without gross rearrangements of these breakpoints show simultaneous overexpression of the PLAG1 and HMGIC genes, i.e. the target genes of the 8q12 and 12q14-15 rearrangements in sporadic adenomas. In addition, one of the tumors expressed a cryptic CTNNB1-PLAG1 fusion transcript. Our findings strongly suggest that identical or very similar molecular mechanisms are operating during adenoma tumorigenesis irrespective of whether the tumors are cytogenetically polyclonal or whether they have non-random, tumor specific abnormalities. Cytogenetically polyclonal adenomas are thus most likely also of monoclonal origin.

A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay

The identification of specific chromosome abnormalities in acute myeloid leukemia (AML) is important for the stratification of patients into the appropriate treatment protocols. However, a significant proportion of diagnostic bone marrow karyotypes in AML is reported as normal by conventional cytogenetic analysis and it is suspected that these karyotypes may conceal the presence of diagnostically significant chromosome rearrangements. To address this question, we have developed a novel 12-color fluorescence in situ hybridization (FISH) assay for telomeric rearrangements (termed M-TEL), which uses an optimized set of chromosome-specific subtelomeric probes. We report here the application of the M-TEL assay to 69 AML cases with apparently normal karyotypes or an isolated trisomy. Of the 69 cases examined, 3 abnormalities were identified, all in the normal karyotype group. The first was a t(11;19)(q23;p13), identified in an infant with AML-M4. In 2 other young patients with AML (< 19 years), an apparently identical t(5;11)(q35;p15.5) was identified. Breakpoint mapping by FISH and reverse transcriptase polymerase chain reaction (RT-PCR) analysis confirmed that this was the same t(5;11) as previously identified in 3 children with AML, associated with del(5q) and resulting in the NUP98-NSD1 gene fusion. The t(5;11) was not detected by 24-color karyotyping using multiplex FISH (M-FISH), emphasizing the value of screening with subtelomeric probes for subtle translocations. This is the first report of the t(5;11)(q35;p15.5) in association with an apparently normal karyotype, and highlights this as a new, potentially clinically significant chromosome rearrangement in childhood AML.