1/15. 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 = 1keywords = hybridization (Clic here for more details about this article) |
2/15. Involvement of the NUP98 gene in a chromosomal translocation t(11;20)(p15;q11.2) in a patient with acute monocytic leukemia (FAB-M5b).We report here a case of acute monocytic leukemia (M5b subtype according to the French-American-British [FAB] classification) with chromosomal translocation t(11;20)(p15;q11.2). fluorescence in situ hybridization analysis with a probe for the NUP98 gene, which is located at chromosome band 11p15, showed that the probe hybridized to both derivative chromosomes 11 and 20 as well as to the remaining normal chromosome 11, indicating that the NUP98 gene was split and involved in this translocation. This is the first report of t(11;20)(p15;q11.2) involving the NUP98 gene in overt leukemia.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/15. A variant form of myelodysplastic syndrome with Ph- minor-BCR/ABL transcript.This study concerns a patient with minor (m)-BCR/ABL transcript-positive and philadelphia (Ph) chromosome-negative myelodysplastic syndrome (MDS). The patient was a 78-year-old man whose condition was diagnosed as refractory anemia with excess of blasts in transformation. Molecular genetic studies, using reverse transcriptase polymerase chain reaction analysis detected m-BCR/ABL messenger rna. We used spectral karyotyping to analyze metaphase cells but could not detect a Ph chromosome. fluorescence in situ hybridization, however, revealed fusion signals of BCR and ABL probes on an apparently normal chromosome 22.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/15. Hyperdiploid karyotype in a childhood MDS patient.We present a rare case of a paediatric myelodysplastic syndrome (MDS) with congenital anomalies (frontal bossing and premature closure of anterior fontanelle). The case showed the clinical and biological features of a refractory anaemia excess blasts (RAEB). bone marrow (BM) cytogenetics demonstrated a hyperdiploid karyotype, with several numerical abnormalities and unidentified rearrangements. fluorescence in situ hybridization (FISH) using chromosome specific alpha-satellite and whole chromosome-specific painting probes verified the hyperdiploid karyotype, and confirmed the origin of the unknown markers and rearrangements more reliably than would be possible using conventional cytogenetic techniques.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/15. Secondary acute myeloid leukaemia with monosomy 7 in identical adult twins.We report the development of secondary acute myeloid leukaemia (AML) with monosomy 7 in identical twins, both at the age of 52 years. In the first twin, induction therapy resulted in complete remission (CR). At relapse 9 months later monosomy 7 was found. The patient died of sepsis 11 months after diagnosis. The other twin presented with leucopenia and thrombocytopenia and refractory anaemia (RA) was diagnosed. During follow-up, fluorescence in situ hybridization analysis demonstrated a monosomy 7 in 11% of the cells. Twenty-eight months following diagnosis the patient progressed to RA with excess blasts in transformation and induction chemotherapy was initiated without achieving CR. Three months later an allogeneic stem cell transplantation from a niece was performed, resulting in CR of the secondary AML.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/15. Clonal eosinophils are a morphologic hallmark of ETV6/ABL1 positive acute myeloid leukemia.BACKGROUND AND OBJECTIVES: The ETV6 gene undergoes rearrangements with tyrosine kinases in hematologic malignancies and solid tumors. ETV6/ABL1 chimeric proteins have been detected both in lymphoid and myeloid disorders. Our objective was to study two new cases of ETV6/ABL1-positive acute myeloid leukemia (AML) and to focus on bone marrow morphology and on molecular cytogenetics of eosinophilic cells. DESIGN AND methods: fluorescence in situ hybridization (FISH) was performed in two AML cases with different translocations, i.e. t(8;12)(p21;p13) and t(9;12) (q34; p13). We used probes for the short arm of chromosome 12, for ABL1 and BCR, for centromeric regions, and for whole chromosome arms. Polymerase chain reaction (PCR) was carried out by applying primers selected for the ETV6 gene. RESULTS: In both cases, bone marrow morphology was characterized by trilineage dysplasia and increased abnormal eosinophils. FISH showed the 5'ETV6 translocated to chromosome 8 in patient #1, and to chromosome 9 in patient #2. A 3' PCR identified chimeric products resulting from fusion between ETV6 exon 4 or exon 5, and ABL1 exon 2. Accordingly, an ETV6/ABL1 fusion signal was detected on der(8) in patient #1, and on der(9) in patient #2. Using interphase FISH abnormal bone marrow eosinophils were proved to belong to the neoplastic clone, carrying the ETV6 rearrangement. INTERPRETATION AND CONCLUSIONS: Our findings provide new information on the heterogeneity of conventional cytogenetics in ETV6/ABL1 positive leukemias, and indicate the putative target cell in this AML is an immature precursor capable of terminally differentiating towards eosinophils.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/15. Different mechanisms lead to a karyotypically identical t(20;21) in myelodysplastic syndrome and in acute myelocytic leukemia.A new t(20;21)(q11;q11), associated with a deletion on the long arm of chromosome 20, was found in one patient with an acute myelocytic leukemia (AML) and in one with myelodysplastic syndrome (MDS). In both cases deletion was interstitial, extending from band q11 to band q13, as shown by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH). FISH analysis with whole arm paints, subtelomeric probes, and locus-specific probes for the long arms of chromosomes 20 and 21 revealed in patient 1 a reciprocal translocation between the deleted 20q and the long arm of chromosome 21, that is, del(20)(q11q13)t(20;21)(q11;q11), and in patient 2, material from 21q was inserted into the deleted 20q, that is, del(20)(q11q13)ins(20;21)(q11;q11q22). This is the first identification of a complex 20;21 rearrangement in MDS/AML. Deletion at 20q and juxtaposition between 20q11 and 21q11 appear to be the critical genomic events.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
8/15. Chromosome 11 rearrangements and specific MLL amplification revealed by spectral karyotyping in a patient with refractory anaemia with excess of blasts (RAEB).A patient with refractory anaemia with excess of blasts (RAEB) had a complex karyotype with multiple markers. spectral karyotyping (SKY) showed rearrangements including three different der(11), containing a very high number of MLL gene copies, shown by fluorescence in situ hybridization (FISH) analysis. Fibre-FISH experiments disclosed the presence of chromatin fibres with multiple MLL copies with a head-to-tail pattern. Apparently, no other region flanking the MLL site was present in the three der(11). MLL amplification was confirmed by the reverse transcription polymerase chain reaction (RT-PCR). The patient died 6 months after diagnosis, supporting the severe prognosis of sole MLL amplification.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/15. trisomy 13 and myelodysplastic syndrome.The clinical and cytogenetic data of a patient with myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB) and trisomy 13 as the sole abnormality are presented. This appears to be only the second report of such a patient. The presence of trisomy 13 is confirmed by in situ hybridization using an alphoid repeat probe L1.26, which is specific for the centromeres of both chromosomes 13 and 21.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/15. Sweet's syndrome in myeloid malignancy: a report of two cases.Two patients with a myeloid malignancy in whom Sweet's syndrome (acute febrile neutrophilic dermatosis) was diagnosed, are described. They suffered from fever and showed cutaneous lesions, with infiltration of the skin by mature neutrophils without signs of vasculitis. In one of them the clonal origin of the infiltrating neutrophils could be demonstrated by in situ hybridization. In this patient an association with the use of recombinant human granulocyte-colony stimulating factor was suspected. In the other patient, Sweet's syndrome was the initial symptom of haematological disease. Inadequate wound healing after surgical procedures led to the diagnosis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
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