Jumping translocations in hematological malignancies: a cytogenetic study of five cases

Manola, Kalliopi N.; Georgakakos, Vasileios N.; Stavropoulou, Chryssa; Spyridonidis, Alexandros; Angelopoulou, Maria K.; Vlachadami, Ioanna; Katsigiannis, Andreas; Roussou, Paraskevi; Pantelias, Gabriel E.; Sambani, Constantina

doi:10.1016/j.cancergencyto.2008.07.010

Cited by 20 publications

(19 citation statements)

References 26 publications

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“…While evidently rare, the incidence of JTs may be under-estimated in our series as cases that were not explicitly reported as a JT would not have been identified. In our JT series, chromosome 1 was the only donor chromosome identified, and this has been most frequently reported in other cases of myeloid malignancy associated with a JT 1, 3, 15 . Chromosome 1 is the largest human chromosome and alterations involving chromosome 1 are frequently found in many types of cancer 16 .…”

Section: Discussionsupporting

confidence: 64%

“…They propose a model suggesting that decondensation may lead to partial endoreplication of the 1q segment resulting in a triradial chromosome 1, which predisposes to cross-over events or translocation of one chromatid to an area of telomeric DNA on another chromosome. Shortening of telomeres on recipient chromosomes has been reported in some cases of JT which may promote fusion with a donor chromosome 15, 22, 23 , although this is not universally described 24 .…”

Section: Discussionmentioning

confidence: 99%

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Jumping Translocations in Myeloid Malignancies Associated With Treatment Resistance and Poor Survival

Sanford

DiNardo

Tang

et al. 2015

Clinical Lymphoma Myeloma and Leukemia

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Background Jumping translocations (JT) are uncommon cytogenetic abnormalities involving non-reciprocal translocations of a single donor chromosome onto two or more chromosomes. The clinical characteristics and prognosis of JTs in patients with myeloid malignancies are not well described. Materials and Methods We searched our cytogenetic database from 2003 to 2014 to identify cases of myeloid malignancies associated with a JT. These cases were cross-referenced with our clinical databases to determine patient characteristics, response to treatment and overall survival. Results We identified 10 patients with myeloid malignancies and a JT: 4 cases of acute myeloid leukemia (AML) with MDS-related changes, 4 cases of myelodysplastic syndrome (MDS) and 2 cases of post-polycythemia myelofibrosis. The donor segment was derived from chromosome 1 in every case. The acquisition of a JT was a late ocurrence, with a median time to JT development of 24.9 months (range 0-248 months) from diagnosis. The overall response to treatment was poor, with no patients achieving a response to conventional chemotherapy or hypomethylating agents. The median overall survival for the group was 9 months (95% CI 2.5-15.5) after identification of a JT. Conclusion The acquisition of a JT in patients with myeloid malignancies appears to be a late event and is associated with myelodysplasia. In our series, this was associated with a poor prognosis with patients having a poor response to treatment, disease transformation to AML and short overall survival.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Jumping Translocations in Myeloid Malignancies Associated With Treatment Resistance and Poor Survival

Sanford

DiNardo

Tang

et al. 2015

Clinical Lymphoma Myeloma and Leukemia

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“…Less than 70 JTs have been reported in hematological malignancies and solid tumors, and only 18 of these have been described in myeloid-lineage hematological disorders. JTs represent secondary changes related to progression of disease and seem to be associated with poor prognosis [Manola et al, 2008;McGrattan et al, 2009]. The underlying mechanism for formation of JTs is not understood, although several mechanisms including viral infections, chromosome instability, shortened telomeres, and illegitimate recombination between telomere repeat sequences have been proposed to explain their formation [Berger and Bernard, 2007].…”

Section: Discussionmentioning

confidence: 99%

Complex Three-Way Translocation Involving MLL, ELL, RREB1, and CMAHP Genes in an Infant with Acute Myeloid Leukemia and t(6;19;11)(p22.2;p13.1;q23.3)

Tuborgh

Meyer

Marschalek

et al. 2013

Cytogenet Genome Res

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Rearrangements affecting the MLL gene in hematological malignancies are associated with poor prognosis. Most often they are reciprocal translocations and more rarely complex forms involving at least 3 chromosomes. We describe an unusual case with cutaneous leukemic infiltrates that waxed and waned until progression to acute myeloid leukemia, AML-M5. The leukemic cells harbored a novel apparent 3-way translocation t(6;19;11)(p22.2;p13.1;q23.3). We utilized advanced molecular cytogenetic methods including 24-color karyotyping, high-resolution array comparative genomic hybridization (aCGH) and DNA sequencing to characterize the genomic complement in the leukemic cells from aspirated bone marrow cells at AML diagnosis. Karyotyping showed 47,XY,t(6;19;11)(p22;p13;q23),+der(6)t(6;11)(p22;q23)[17]/48,sl,+8[3]/48,sl,+8,der(12)t(1;12)(q11;p13)[3]/ 48,sdl,der(Y)t(Y;1)(q12;q11),+8[7] conferring MLL-ELL fusion. Oligo-aCGH analysis confirmed gains of 6p22qter and 11q23.3qter involving the CMAHP and MLL genes, respectively. DNA sequencing disclosed an additional breakpoint at 6p24.3 (at RREB1 gene). Retrospective fluorescence in situ hybridization revealed presence of the MLL-involving rearrangement in the initial stages of disease before clear morphological signs of bone marrow involvement. The patient responded well to therapy and remains in remission >6 years from diagnosis. This apparent 3-way translocation is remarkable because of its rarity and presentation with myeloid sarcoma, and may, as more cases are characterized, further our understanding onto how such complex translocations contribute to promote leukemogenesis and respond to therapy.

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“…It is seen in all ages and appears to be associated with a dismal prognosis (3,4). Nevertheless, survivals longer than 36 months have been reported in 3 childhood cases one of which was an ALL (4–6). The same fusion FUS/ERG has also been found in 3 Ewing tumors (8,9); it is thus one of the relatively few fusion genes that exert pathogenetic influence in widely disparate neoplastic entities.…”

Section: Introductionmentioning

confidence: 99%

Cryptic FUS-ERG fusion identified by RNA-sequencing in childhood acute myeloid leukemia

et al. 2013

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Sequential combination of cytogenetics and RNA-sequencing (RNA-Seq) has been shown to be an efficient approach to detect pathogenetically important fusion genes in neoplasms carrying only one or a few chromosomal rearrangements. We performed RNA-Seq on an acute myeloid leukemia in a 2-year-old girl with the karyotype 46,XX,add(1)(p36), der(2)t(2;3)(q21;q21),del(3)(q21),der(10)t(1;10)(q32;q24),der(16)(2qter-->2q21::16p11-->16q24::16p11-->16pter)[13]/46,XX[2] and identified a cryptic FUS/ERG fusion gene. PCR and direct sequencing verified the presence of the FUS-ERG chimeric transcript in which exon 7 of FUS from 16p11 (nt 904 in sequence with accession number NM_004960 version 3) was fused in frame to exon 8 of ERG from sub-band 21q22.2 (nt 967 in NM_004449 version 4). The FUS-ERG transcript found here has been reported in only two other cases of childhood leukemia, in a 1-year-old boy and an 8-month-old boy, both diagnosed with precursor B cell ALL. The fusion transcript codes for a 497 amino acid residues FUS-ERG protein and, similar to other AML-related FUS-ERG fusion proteins, contains both functional domains (TR1 and TR2) of the transactivation domain of FUS and the ETS domain of ERG. The clinical significance, if any, of the amino acid residues which are coded by the exons 8, 9 and 10 of ERG in the fusion FUS-ERG proteins, remains unclear.

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Jumping translocations in hematological malignancies: a cytogenetic study of five cases

Cited by 20 publications

References 26 publications

Jumping Translocations in Myeloid Malignancies Associated With Treatment Resistance and Poor Survival

Jumping Translocations in Myeloid Malignancies Associated With Treatment Resistance and Poor Survival

Complex Three-Way Translocation Involving <b><i>MLL</i></b>, <b><i>ELL</i></b>, <b><i>RREB1</i></b>, and <b><i>CMAHP </i></b>Genes in an Infant with Acute Myeloid Leukemia and t(6;19;11)(p22.2;p13.1;q23.3)

Cryptic FUS-ERG fusion identified by RNA-sequencing in childhood acute myeloid leukemia

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