A case of pediatric B-Lymphoblastic leukemia presenting with a t(9;12)(p24;q11.2) involving JAK2 and concomitant MLL rearrangement with apparent insertion at 6q27
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B-cell acute lymphoblastic leukemia (B-ALL) is the most common malignancy in pediatric patients and the leading cause of cancer-related death in children and young adults. Translocations of 9p24 involving JAK2 (9p24) and gain-of-function mutations of JAK2 with subsequent activation of the JAK2 kinase have been described in several hematological malignancies including B-ALL. However, rearrangements involving JAK2 are rare in B-ALL as only few cases have been described in the literature.Herein, we present a case of pediatric B-ALL whose conventional cytogenetics revealed an abnormal karyotype with a reciprocal translocation involving 9p24 (JAK2) and 12p11.2. Fluorescence in situ hybridization (FISH) studies using the RP11-927H16 Spectrum Green JAK2 probe on previously G-banded metaphases confirmed the involvement of JAK2 in this rearrangement. Further FISH studies on the same previously G-banded metaphases using the LSI MLL probe helped to characterize an insertion of MLL into 6q27 as an additional abnormality in this karyotype. FISH studies performed on interphase nuclei also revealed an abnormal clone with MLL rearrangements in 23.6% of the nuclei examined as well as an abnormal clonal population with a deletion of the 5'IGH@ region in 88.3% of the nuclei examined.Rearrangements of 9p24 can result in constitutive activation of JAK2, and have been observed in B-ALL. Rearrangements of the MLL gene have also been described extensively in B-ALL. However, rearrangements of MLL with a partner at 6q27 and in conjunction with a translocation involving JAK2 have not been previously described. This case pinpoints the importance of FISH and conventional cytogenetics to characterize complex rearrangements in which JAK2 and MLL are involved. The therapeutic targeting of JAK2 and MLL in cases like this may be prognostically beneficial.Keywords:
clone (Java method)
Gene rearrangement
Summary. Translocations involving the MLL gene on the chromosome 11 (11q23) are frequently observed in acute leukaemia. The detection of this genetic change has a unique significance as a result of its implication of poor prognosis. To reveal the utility of fluorescence in situ hybridization (FISH) in detecting the MLL translocation, we analysed 289 consecutive Korean patients (children and adults) with acute leukaemias using both conventional cytogenetic analysis (CC) and FISH, placing an emphasis on the result discrepancies. Twenty‐two of 289 patients (7·6%) had the 11q23/ MLL translocation. In nine of 22 patients (41%), only FISH detected the translocation. In eight of these 22 patients, a total of 19 follow‐up examinations were performed, of which FISH detected a significant level of leukaemic cells harbouring the MLL translocation in five patients (26%) without cytogenetic evidence. In addition to the MLL translocation, FISH detected submicroscopic amplification, partial deletion of the MLL gene and trisomy 11 in 12 patients without cytogenetic evidence. In summary, up to 41% of the MLL translocations at initial work‐up and 26% during follow‐up were detected by FISH without cytogenetic evidence. Thus, we recommend that MLL FISH should be performed in the diagnosis and monitoring of acute leukaemias in combination with CC.
Trisomy
Trisomy 8
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Acute myeloid leukemia associated with translocation t(8;21) and the underlying AML1-ETO gene fusion is considered as a distinct type of leukemia with characteristic morphologic features. Variant and masked forms of the classic translocation t(8;21) are uncommon and their clinicopathologic features are less well characterized. We report here a patient with a masked translocation involving chromosomes 6,8 and 21. Chromosomal study at diagnosis initially reported the karyotype as translocation between chromosomes 6 and 8 without visible involvement of chromosome 21. However, fluorescence in situ hybridization studies revealed the involvement of chromosome 21 in the translocation and presence of the AML1-ETO chimeric gene. The complex rearrangement t(6;8;21) observed in our patient was not previously described and could be not detected without combination of techniques. Our case illustrates the challenge of recognizing complex aberrations that occur with variant t(8;21) and further reinforces the utility of fluorescence in situ hybridization applications in more accurate characterization of chromosome abnormalities which can lead to more precise therapeutic stratification.
Chromosomal rearrangement
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To assess the value of eight-probe fluorescence in situ hybridization (FISH) and R-banding karyotype analysis for the diagnosis of acute lymphoblastic leukemia (ALL).With the eight-probe FISH (using probes for MYC, P16, E2A, CHIC2/D10Z1/D17Z1, TEL/AMLl, MLL, BCR/ABL1, and IGH) and R-banding karyotype analysis, 237 cases of ALL were analyzed.Cytogenetic changes were detected in 135 (56.96%) of all cases, which have involved MYC, P16, E2A, CHIC2/D10Z1/D17Z1, TEL/AMLl, MLL, BCR/ABL1, and IGH polyploidies. R-banding karyotype analysis has only detected abnormalities in 48 of such cases, in addition with 14 abnormalities missed by the FISH probes, which have given a total positive rate of 26.16%. The detection rate of the two methods has differed significantly(P<0.05).Compared with the R-banding karyotype analysis, the eight-probe FISH is more accurate and efficient. Diagnosis of cytogenetic abnormalities for children with ALL using the combined method can provide a basis for evaluation of prognosis as well as personalized therapy.
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Multiple myeloma (MM) is a genetically heterogeneous disease, with cytogenetic findings that determine disease behavior. Genetic abnormalities can be assessed by fluorescence in situ hybridization (FISH) analysis and/or G-banded karyotyping. The two methods produce unique and overlapping information, and the clinical utility of using both is investigated here.Seventy patients diagnosed with MM at a hospital in Southern California were retrospectively reviewed for the FISH and G-banded karyotyping results obtained from bone marrow specimens.Karyotype was normal in 71% (50/70), abnormal in 27% (19/70), and inadequate in 1% (1/70). Among patients with abnormal karyotype, FISH provided additional information about genetic aberrations in 95% of cases (18/19). Among cases with abnormal FISH, karyotype provided additional information about genetic aberrations in 27% of cases (18/66). When numerical abnormalities were present (detected by FISH and/or karyotype), FISH detected them in 95% (54/57), of which karyotype missed 70% (38/54) of the time. Karyotyping detected numerical abnormalities in 33% (19/57), which FISH missed 16% (3/19) of the time.Karyotyping and FISH analysis in MM each provide unique information. For most patients, performing both tests together will provide more information than either test alone.
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To investigate the common chromosome abnormalities of the patients with multiple myeloma in China and the relationships of cytogenetic abnormalities and clinical features.In interphase fluorescence in-situ hybridization (FISH) analysis, a panel of probes including D13S319 (13q14.3), RB1(RB1 gene), IgH (14q32), P53(17p13), 1q21(1q21 gene) was used to study the cytogenetic abnormalities of 31 patients with multiple myeloma; and the clinical implications of cytogenetic abnormalities were investigated.The frequencies of the partial deletion of chromosome 13, translocation involving the 14q32 region, abnormalities in 1q21 and deletion of 17p13 were 45%, 68%, 50%, and 35% in the study, respectively. The abnormalities of both the partial deletion of chromosome 13 and translocation involving the 14q32 region were found in 35% of the patients. 79% of the patients with del (13q) had 14q32 translocations simultaneously. All the patients with positive detection of probe D13S319 were found to have translocation of 14q32 at the same time. There were correlations between the partial deletion of chromosome 13 and translocation involving the 14q32 region. The overall response rate of induction treatment was 67.7%. No significant difference was found in patients with positive or negative cytogenetic abnormalities of del(13q), 14q32 translocation, del(17p13), and 1q21 abnormalities.13q deletion, IgH rearrangement, chromosome 1 abnormality and 17p13 deletion are the common cytogenetic abnormalities of MM patients in China. There is a significant correlation between the presence of 14q32 translocations and chromosome 13 deletion in MM patients.
Chromosome 13
Chromosome abnormality
Interphase
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Objective To investigate the translocation of IgH gene at chromosome 14q32 in chronic lymphocytic leukemia ( CLL) and explore the relationship between the IgH gene translocation and progression of CLL Methods IGHC and IGHV DNA specific probes for IgH gene and interphase fluorescence in situ hybridization (FISH) were used for detecting the IgH gene translocation in 70 patients with newly diagnosed B cell CLL (B-CLL). Results Out of the 70 patients, the IgH gene translocation was found in 8 patients (11. 4% ) with the rate of IgH translocation cells ranging from 10. 5% to 53. 0%. There was no significant difference in the IgH gene translocation either between two sexes or among ages or Binet stages (P 0. 05). Conclusion The IgH translocation is a frequent event in B-CLL, and further investigation of the effect of the IgH translocation on the pathogenesis and progression of B-CLL is needed. FISH is a rapid, exact and sensitive technique in analysis of IgH gene translocation in CLL
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Summary. The detection of chromosomal translocations by fluorescence in situ hybridization (FISH) is widely performed, but very few studies have attempted to apply this technique to paraffin‐embedded routine biopsy samples. We report the analysis of paraffin sections from 36 B‐cell lymphoma biopsies for MYC translocation breakpoints by FISH. The probes consisted of multi‐YAC constructs that flanked the breakpoint region and that, therefore, separate upon a chromosomal translocation and generate split (or ‘segregated’) signals (rather than a more ambiguous ‘co‐localization’ pattern, obtained when the two partners in a hybrid gene are detected). The results were assessed by a simple approach that avoids the counting of signal numbers per nucleus and so is appropriate for use in routine practice. A total of 19 of the 36 lymphomas were scored as positive for MYC translocation and this included 16 of the 20 patients in whom classic cytogenetics had shown the presence of the (8;14) translocation (or one of its two variants). We conclude that this two‐colour ‘split‐signal’ technique based on breakpoint flanking probes can readily detect chromosomal translocations in paraffin sections. Furthermore, our results suggest that cases categorized as ‘atypical Burkitt’s/Burkitt‐like' lymphoma (at least for adult patients) are heterogeneous with respect to translocations involving the MYC oncogene, as well as immunophenotype and clinical features.
Breakpoint
Immunophenotyping
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Objective To study long\|term radiation effect in occupational workers exposed to low dose X\|rays using the method of fluorescence in situ hybridization(FISH). Method Chromosome translocations of 25 medical X\|ray workers were analyzed by FISH with chromosome 4\+# and 7\+# probes according to PAINT (The Protocol for Aberration Identification and Nomenclature Terminology) system. Results The frequency of genome translocation in X\|ray workers was (13 14±1 23)/1 000 cells.The rate of complete and incomplete translocation was 1∶1 7.According to the calendar year of entry before/after the year of 1965 as the border,the data showed that the incomplete translocation of the after 1965 group was higher than that of the controls ( P 0 05) and the complete and incomplete translocations of the before 1965 group were obviously higher than those of the controls ( P 0 01 and P 0 05,respectively). Conclusion The chromosome translocation in early Chinese medical X\|ray workers is mainly the incomplete one,the frequency of translocation does not dependent on chromosomal DNA content,and incomplete and comple ones increase along with prolongation of working years in their position.
Derivative chromosome
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