Complex Chromosome 9, 20, and 22 Rearrangements in Acute Lymphoblastic Leukemia with Duplication of BCR and ABL Sequences

Stevens‐Kroef, Marian; Dirckx, R.; Meers, L E C; Albrechts, J. C. M.; Schouten, Harry C.; Hamers, A.J.H.

doi:10.1016/s0165-4608(99)00119-3

Cited by 4 publications

(4 citation statements)

References 13 publications

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“…(B) The HsD4 is flanked by numerous repeats similar to these flanking the breakpoint cluster region (BCR) gene (Figure S11). The human BCR gene is located at the site of the translocation breakpoint found in chronic myeloid leukemia [32], which like Smith-Magenis region is a “hot-spot” for recombination. (C) The mRNA sequences of D1C, D3A, D4 and D5 genes in human and mouse contain TEs (table S2).…”

Section: Resultsmentioning

confidence: 99%

Ancient Origin of the New Developmental Superfamily DANGER

et al. 2007

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Developmental proteins play a pivotal role in the origin of animal complexity and diversity. We report here the identification of a highly divergent developmental protein superfamily (DANGER), which originated before the emergence of animals (∼850 million years ago) and experienced major expansion-contraction events during metazoan evolution. Sequence analysis demonstrates that DANGER proteins diverged via multiple mechanisms, including amino acid substitution, intron gain and/or loss, and recombination. Divergence for DANGER proteins is substantially greater than for the prototypic member of the superfamily (Mab-21 family) and other developmental protein families (e.g., WNT proteins). DANGER proteins are widely expressed and display species-dependent tissue expression patterns, with many members having roles in development. DANGER1A, which regulates the inositol trisphosphate receptor, promotes the differentiation and outgrowth of neuronal processes. Regulation of development may be a universal function of DANGER family members. This family provides a model system to investigate how rapid protein divergence contributes to morphological complexity.

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Section: Resultsmentioning

confidence: 99%

Ancient Origin of the New Developmental Superfamily DANGER

et al. 2007

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“…In a Ph negative but BCR‐ABL positive CML case, Morris et al (1991) described a complex t(9;20;22)(q34;p13;q11) postulated as a two step event with the BCR‐ABL fusion gene on the short arm of chromosome 20, however, no duplication of the fusion gene was observed, as seen in the present three cases with dic(20;Ph). Stevens‐Kroef et al (2000) recently reported a case of Ph‐positive acute lymphoid leukaemia (ALL) in which extra copies of the BCR‐ABL fusion gene were located on two small marker chromosomes, which by conventional karyotyping appeared ‘similar in size but with different primary constrictions’. Both markers belonged to a cell clone which carried a der(9)t(9;22)(q34;q11), one copy of both 20 and 22 homologues but no Ph chromosome.…”

Section: Discussionmentioning

confidence: 99%

Double Philadelphia masquerading as chromosome 20q deletion – a new recurrent abnormality in chronic myeloid leukaemia blast crisis

et al. 2003

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Summary. The most common abnormality of chromosome 20 in haematological malignancy is deletion of the long arm [del(20q)]. These interstitial deletions are variable in size and are seen in both premalignant haematological conditions and acute myeloid neoplasia. A commonly deleted region (CDR), mapped within the 20q11.2/q13.1 segment with an estimated size of 1AE7 Mbp, is considered to present a primary genetic lesion marking a gene(s), the loss of which is responsible for the pathogenesis of these haematological disorders. While a small number of recurrent translocations involving chromosome 20 have also been reported, no recurrent aberration of this chromosome has been associated with myeloid disease progression. We present nine cases of Philadelphia (Ph)-positive chronic myeloid leukaemia (CML) in which deletions of chromosome 20 were also detected by conventional karyotyping. In six cases, fluorescent in situ hybridization (FISH) mapping confirmed a del(20q) which corresponded to the myeloid CDR. In the remaining three cases however, the presumed del(20q) marker was shown to be the result of an unbalanced translocation between band 20p11 and a second copy of the Ph chromosome. This new abnormality, termed dic(20;Ph) for short, was identical to a del(20)q by G-banding, and combined duplication of the breakpoint cluster region and Abelson murine leukaemia viral oncogene homologue (BCR-ABL) fusion with loss of the 20p11-pter segment. In all three cases, the dic(20;Ph) was associated with disease progression and therefore represents a new recurrent abnormality in CML blast crisis.

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“…The outcome reported in this study can be considered exemplary for those in the other studies listed in Table 1. Whereas the remission rate was 79% in the unfavorable cytogenetic group (vs. 80% remission rate overall), the median disease‐free survival (DFS) was only 11 months with a probability of staying in continuous remission at 5 years of only 8% when compared to a median DFS of 2.3 years and a probability of continuous remission at 5 years of 38% in patients with diploid karyotypes and up to 4.7+ years and more than 75%, respectively, in patients with more favorable karyotypes such as del (12) or translocations involving chromosome 14q. The same results are true for survival where the probability of being alive with Ph‐positive ALL at 5 years is 11% compared to 37% for patients with diploid karyotypes.…”

Section: Therapeutic Approaches To Ph‐positive Allmentioning

confidence: 99%

“…Variant and complex Ph translocations are described (12). Novel BCR‐ABL transcripts with unusual breakpoints such as e19a2 or e1a3, or insertion of ABL sequences between BCR and ABL exons are found in rare cases (13, 14).…”

Section: The Philadelphia Translocation and Its Molecular Correlatesmentioning

confidence: 99%

Philadelphia chromosome‐positive acute lymphoblastic leukemia– current concepts and future perspectives

Faderl

Garcia‐Manero

Thomas

et al. 2002

Rev Clin Exp Hematol

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Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) is diagnosed rarely in children, but constitutes the most frequent cytogenetic abnormality in adults with ALL. In contrast to chronic myeloid leukemia (CML), patients with Ph-positive ALL usually demonstrate expression of a truncated version of the BCR-ABL protein called p190bcr-abl. Irrespective of age and breakpoint location, Ph-positive ALL carries a poor prognosis. Although remission rates are identical to those of Ph-negative ALL, relapse is almost universal and long-term survival remains rare. Given the poor outcome with current chemotherapy consolidation programs, stem cell transplantation is usually recommended for these patients in first remission or as soon as feasible. Even with transplantation the impact on outcome is limited and new therapeutic concepts are urgently needed. One of the most promising developments in recent years has been the introduction of the tyrosine kinase inhibitors such as STI571. An overview of current treatment modalities in Ph-positive ALL will be provided and the rationale for new therapies will be discussed.

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Complex Chromosome 9, 20, and 22 Rearrangements in Acute Lymphoblastic Leukemia with Duplication of BCR and ABL Sequences

Cited by 4 publications

References 13 publications

Ancient Origin of the New Developmental Superfamily DANGER

Ancient Origin of the New Developmental Superfamily DANGER

Double Philadelphia masquerading as chromosome 20q deletion – a new recurrent abnormality in chronic myeloid leukaemia blast crisis

Philadelphia chromosome‐positive acute lymphoblastic leukemia– current concepts and future perspectives

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