1/32. Variant three-way translocation of inversion 16 in AML-M4Eo confirmed by fluorescence in situ hybridization analysis.The inv(16) and t(16;16) characterize a subgroup of acute myelomonocytic leukemia (AML) with distinct morphological features and a favorable prognosis. Both cytogenetic abnormalities result in a fusion of CBF beta at 16q22 and MYH11 gene at 16p13, whose detection by PCR and fluorescence in situ hybridization (FISH) is useful for diagnosis and monitoring of the disease. Variant translocations of inv(16)/t(16;16) are very rare and whether they are also associated with a favorable prognosis is unknown. We report a patient presenting with typical AML-M4Eo and a three-way translocation of inv(16) involving 16p13, 16q22, and 3q22. FISH studies on bone marrow (BM) chromosomes using CBFB and MYH11 dna probes revealed a fusion of CBFB and MYH11 on 16q of the der(16), as well as a signal from MYH11 on 16p but not from CBFB; normal signals for both probes were present on the normal 16. Neither of these labeled probes was on the der(3), but the translocation between the der(3) and der(16) was confirmed by using a chromosome 16 painting probe. Molecular analysis of BM cells using RT-PCR identified a CBFB-MYH11 fusion transcript type D. After achieving complete remission, the patient relapsed. We conclude that FISH and PCR are feasible tools to distinguish cases with variant abnormalities of inv(16) from cases with other chromosome 16 abnormalities. Variant abnormalities of inv(16) may be not associated with favorable prognosis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/32. A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer cytogenetics Group (UKCCG)Partial deletion of the long arm of chromosome 5, del(5q), is the cytogenetic hallmark of the 5q-syndrome, a distinct subtype of myelodysplastic syndrome-refractory anemia (MDS-RA). Deletions of 5q also occur in the full spectrum of other de novo and therapy-related MDS and acute myeloid leukemia (AML) types, most often in association with other chromosome abnormalities. However, the loss of genetic material from 5q is believed to be of primary importance in the pathogenesis of all del(5q) disorders. In the present study, we performed fluorescence in situ hybridization (FISH) studies using a chromosome 5-specific whole chromosome painting probe and a 5q subtelomeric probe to determine the incidence of cryptic translocations. We studied archival fixed chromosome suspensions from 36 patients with myeloid disorders (predominantly MDS and AML) and del(5q) as the sole abnormality. In 3 AML patients studied, this identified a translocation of 5q subtelomeric sequences from the del(5q) to the short arm of an apparently normal chromosome 11. FISH with chromosome 11-specific subtelomeric probes confirmed the presence of 11p on the shortened 5q. Further FISH mapping confirmed that the 5q and 11p translocation breakpoints were the same in all 3 cases, between the nucleophosmin (NPM1) and fms-related tyrosine kinase 4 (FLT4) genes on 5q35 and the Harvey ras-1-related gene complex (HRC) and the radixin pseudogene (RDPX1) on 11p15.5. Importantly, all 3 patients with the cryptic t(5;11) were children: a total of 3 of 4 AML children studied. Two were classified as AML-M2 and the third was classified as M4. All 3 responded poorly to treatment and had short survival times, ranging from 10 to 18 months. Although del(5q) is rare in childhood AML, this study indicates that, within this subgroup, the incidence of cryptic t(5;11) may be high. It is significant that none of the 24 MDS patients studied, including 11 confirmed as having 5q-syndrome, had the translocation. Therefore, this appears to be a new nonrandom chromosomal translocation, specifically associated with childhood AML with a differentiated blast cell phenotype and the presence of a del(5q).- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
3/32. Chromosome 16 inversion-associated translocation: two new cases.Two patients with chromosome 16 inversion-associated translocation were studied with conventional cytogenetic and fluorescence in situ hybridization (FISH) techniques. The same chromosome 16 was involved in inversion and translocation in both patients. The chromosome translocation breakpoint was located within the heterochromatin of chromosome 16 but outside the alpha satellite domain in the t(10;16) of the first patient, whereas it was outside the heterochromatin area in the second case with t(1;16). These two types of rearrangements may be due to different mechanisms and illustrate the possible difficulties in recognizing the chromosome 16 inversion without FISH studies.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
4/32. trisomy 11 and a complex t(11;11;22) in a patient with acute myelomonocytic leukemia (AML-M4) following myelodysplasia (MDS): a cytogenetic study of a mechanism of leukemogenesis.We describe a 73-year-old man diagnosed with acute myelomonocytic leukemia (AML-M4) following myelodysplasia with trisomy 11 and with a t(11;11;22). This is the first case with both abnormalities present in the same cells and with the t(11;11;22) involving a chromosome 11 already duplicated at 11q23. This band contains the MLL gene that undergoes partial tandem duplication in patients with 11, which is "promiscuous," being translocated with a large number of genetic partners. Our patient had a complex karyotype that was completely defined by in situ hybridization. This technique demonstrated that the t(11;11;22) derivative with a duplication of band 11q23 carried from three to four copies of MLL. Two copies of the gene were close to each other and centromeric to the break-point region. Therefore, a partial tandem duplication of the MLL gene might have happened before the occurrence of t(11;11;22). Considering the associated chromosome defects, the monosomy for the long arm of chromosome 7, due to an unbalanced translocation t(7;17), further underlines the possibility that a partial tandem duplication of the MLL gene might have taken place.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
5/32. 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.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
6/32. Morphological and cytogenetic changes in therapy-related leukemia developed in a t(8;21)-acute myeloid leukemia (M2) patient: sequential cytogenetic and molecular analyses.A patient with acute myeloid leukemia (AML)-M2 with t(8;21)(q22;q22) achieved complete remission with remission-induction chemotherapy followed by consolidation and intensification chemotherapies. T(8;21)(q22;q22) disappeared, but chimeric AML1/MTG8 was continuously detected in bone marrow cells. Following the development of therapy-related leukemia after 1 year, evolution of therapy-related AML-M4 with t(11;17)(q23;q25) and the rearrangement of the MLL gene were observed, while AML/MTG8 disappeared. After reinduction and following intermittent chemotherapies, a subsequent alternative transformation to AML-M2 occurred after detection of t(3;21)(q21;q22), with a break in the AML1 gene shown by interphase fluorescence in situ hybridization analysis. This leukemia transformed to AML-M4 after t(9;22)(q34;q11), with a minor BCR/ABL rearrangement, and then finally to AML-M2. This therapy-related leukemia was resistant to chemotherapy. These findings indicate that alterations in cytogenetic and molecular events caused by chemotherapeutic agents contribute to the sequential evolution of new leukemic clones with different morphology.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
7/32. Nonrandom rearrangements of 6p in malignant hematological disorders.It is very uncommon to observe nontranslocation abnormalities (NTAs) involving the short arm of chromosome 6 (6p) in malignant hematological disorders (MHDs). By using conventional cytogenetics and fluorescence in situ hybridization (FISH) with chromosome-microdissection probes specific for 6p21 and 6p25, we observed five patients with myeloid malignancies and two patients with lymphoid malignancies to have 6p NTAs. On the basis of our data and those in the literature, it is possible to divide 6p NTAs into the following three groups in MHD: The first group presents with 6p NTAs as a sole or primary change in myeloid malignancies. There are only two cases reported in this group, including one case with del(6)(p23) and the present case with ins(6)(q23p23p25) identified by FISH only. The second group presents with 6p deletions as a sole or primary change in lymphoid malignancies. Three cases have been reported in this group, including one case with del(6)(p21p23), one with del(6)(p21), and the present case 2 with del(6)(p21). The third group has 6p deletions in addition to other known primary changes, present in both myeloid and lymphoid disorders, with 36 cases reported, including five cases from our series. Deletions involving 6p21, 6p22, or 6p23 have been observed in both myeloid and lymphoid disorders. The present data provide cogent information for further molecular characterization of 6p anomalies in MHD.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
8/32. CBFB/MYH11 fusion in a patient with AML-M4Eo and cytogenetically normal chromosomes 16.We present a unique case of acute myeloid leukemia M4Eo (AML-M4Eo) with a CBFB/MYH11 fusion transcript and a trisomy 22, but in whom cytogenetic analyses did not disclose an inv(16). fluorescence in situ hybridization (FISH) analysis with chromosome arm-specific painting probes as well as with the c40 and c36 cosmids also revealed no evidence for an inv(16), whereas the application of locus-specific probes confirmed the presence of a masked inv(16). The results of our comprehensive FISH investigations indicate that the events leading to this masked inv(16) were complex and concurred with deletions on both the long and short arms. The most likely explanation for the formation of the relevant CBFB/MYH11 fusion is an insertion of parts of the MYH11 into the CBFB gene, although it is also possible that it was formed by a double inversion.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
9/32. Translocation (8;16) in a patient with acute myelomonocytic leukemia, occurring after treatment with fludarabine for a low-grade non-Hodgkin's lymphoma.We describe a 65-year old woman who developed a t(8;16)(p11;p13) positive acute myeloid leukemia (AML)-M4 without a prior myelodysplasia thirty-six months after a low-grade non-Hodgkin's lymphoma treated with alkylating agents (chlorambucil and cyclophosphamide) and fludarabine, a purine analog with a significant activity in lymphoproliferative disorders. The t(8;16)(p11;p13) is present in 0.4% of AML of M4-M5 cytotype. In the present case it was identified by conventional cytogenetics; involvement of the MOZ and CBP genes was demonstrated by fluorescence in situ hybridization, but not by reverse transcription polymerase chain reaction. The patient died of sepsis after the first course of induction chemotherapy. This is the first t(8;16) AML-M4 arising after fludarabine treatment of which the leukemogenic role in our case is very difficult to ascertain. Most t(8;16) t-AML cases had received anthracyclines with or without cyclophosphamide; none was ever administered chlorambucil. Our patient was never given anthracyclines and the cumulative doses of chlorambucil and cyclophosphamide employed were low.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
10/32. Isodicentric 7p, idic(7)(q11.2), in acute myeloid leukemia associated with older age and favorable response to induction chemotherapy: a new clinical entity?Three adult de novo acute myeloid leukemias (AML M1, M2, and M4) with an isochromosome 7p are presented. No additional abnormalities were detected by G-band and multicolor, using combined binary ratio labeling, fluorescence in situ hybridization (FISH) analyses, indicating that the i(7p) was the sole, i.e., the primary, chromosomal aberration. Although the patients were elderly--68, 72, and 78 years old--they all responded very well to chemotherapy, achieving complete remission lasting more than a year. Further FISH analyses, using painting, centromeric, as well as 7q11.2-specific YAC probes, revealed that the i(7p) contained two centromeres and that the breakpoints were located in 7q11.2. Thus, the abnormality should formally be designated idic(7)(q11.2). The detailed mapping disclosed a breakpoint heterogeneity, with the breaks in 7q11.2 varying among the cases, being at least 1,310 kb apart. Furthermore, the breakpoints also differed within one of the cases, being located on both the proximal and the distal side of the most centromeric probe used. Based on our three patients, as well as on a previously reported 82-year-old patient with AML M2 and idic(7)(q11) as the only chromosomal change, we suggest that this abnormality, as the sole anomaly, is associated with AML in elderly patients who display a good response to induction chemotherapy and, hence, have a favorable prognosis. Furthermore, the heterogeneous breakpoints in 7q11.2 suggest that the important functional outcome of the idic(7)(q11.2) is the genomic imbalance incurred, i.e., gain of 7p and loss of 7q material, rather than a rearrangement of a specific gene.- - - - - - - - - - ranking = 0.2keywords = hybridization (Clic here for more details about this article) |
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