Isochromosomes in acute lymphoblastic leukaemia: I(21q) is a significant finding

Martineau, Mary; Clark, Roslyn; Farrell, Dianna M.; Hawkins, Jacqueline M.; Moorman, Anthony V.; Secker-Walker, LM

doi:10.1002/(sici)1098-2264(199609)17:1<21::aid-gcc4>3.0.co;2-4

Cited by 32 publications

(17 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…deletions of the second ETV6 allele, is in agreement with previous studies showing that this is frequent in childhood ALL with t(12;21) (Raynaud et al, 1996). One reason for this may be that expression of wildtype ETV6 interferes with ETV6/CBFA2 leukaemogenicity (Hiebert et al, 1996).A similar ider(21) was recently reported in one case of childhood ALL (Martineau et al, 1996), suggesting that this is a new recurrent abnormality resulting in ETV6/CBFA2 fusion. Since ider(21) is cytogenetically indistinguishable from i(21)(q10) and idic(21)(p11) -other recurrent aberrations associated with similar clinical features as the t(12;21), i.e.…”

supporting

confidence: 53%

“…Since ider(21) is cytogenetically indistinguishable from i(21)(q10) and idic(21)(p11) -other recurrent aberrations associated with similar clinical features as the t(12;21), i.e. pre-B-cell ALL and age 1-10 years (Mitelman, 1994 updated;Martineau et al, 1996) -molecular investigations of ALL with these changes may reveal an ETV6/CBFA2 fusion. Therefore we suggest that this chimaeric transcript should be actively sought, not only in cases with del(12p), but also in childhood ALL with i(21)(q10) and idic (21) left, simultaneous hybridization of the ETV6 (green signal) and CBFA2 (red signal) YACs in a metaphase.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Childhood acute lymphoblastic leukaemia with ider(21)(q10)t(12;21)(p12;q22): a new recurrent abnormality showing ETV6/CBFA2 fusion

Andreasson¹,

Johansson²,

Strömbeck³

et al. 1997

Br J Haematol

View full text Add to dashboard Cite

Summary. The cytogenetically unidentifiable t(12;21) (p12;q22), resulting in ETV6/CBFA2 fusion, is the most frequent chromosomal aberration in childhood acute lymphoblastic leukaemia (ALL). We report a variant, ider(21) (q10)t(12;21)(p12;q22), which was shown to contain double ETV6/CBFA2 fusions by fluorescence in situ hybridization. This is the second case of such an ider(21) in childhood ALL, suggesting that it is a new recurrent abnormality. Since the ider(21) is cytogenetically indistinguishable from i(21)(q10) and idic(21)(p11), changes associated with similar clinical features as the t(12;21), i.e. pre-B-cell ALL and age 1-10 years, we suggest that all ALL displaying these changes should be tested for ETV6/CBFA2 fusion transcript. Keywords: childhood ALL, cytogenetics, FISH, ETV6/CBFA2.The t(12;21)(p12;q22) is present in 20-30% of childhood acute lymphoblastic leukaemia (ALL), making it the single most frequent chromosomal abnormality in this setting (Romana et al, 1995b;Liang et al, 1996). The patients are usually between 1 and 10 years old, display a pre-B-cell ALL, and seem to have a favourable, or even excellent, prognosis (Shurtleff et al, 1995;Liang et al, 1996). Since the breakpoints at chromosomes 12 and 21 are located in similarly lightstaining telomeric bands, this translocation is unidentifiable with standard banding techniques. However, using fluorescence in situ hybridization (FISH) the aberration is readily seen. At the molecular level, the translocation has been shown to result in fusion between the ETV6 and CBFA2 genes (previously TEL and AML1, respectively) (Golub et al, 1995;Romana et al, 1995a).A 6-year-old boy was admitted to hospital due to pain in the legs and fever. Peripheral blood showed a white cell count of 3 : 2 × 10 9 /l, haemoglobin of 6 . 9 g/dl and thrombocytes of 52 × 10 9 /l. Hepatosplenomegaly was noted on clinical examination. Morphological and immunophenotypical bone marrow investigations revealed a pre-B-cell ALL of FAB L1/ L2 subtype. Cytogenetic studies showed a pseudodiploid karyotype: 46,XY,del(12)(p12),i(21)(q10).FISH was performed, as previously described (Andreasson et al, 1997), with whole chromosome painting (wcp) probes for chromosomes 12 and 21. This analysis not only verified the i(21q) but also disclosed a der(12) with chromosome 21 material at the end of the p-arm, suggesting a cryptic t(12;21). Further FISH experiments were performed with YAC probes 964c10 and 958b8, covering the ETV6 gene (Kobayashi et al, 1994) and cosmids 179a6, 163e7 and 244e8, specific for the same gene . CBFA2 rearrangement was detected with five overlapping YAC probes: 812f11, covering the CBFA2 breakpoint, 464h8 and 613e10 located telomeric, and 72h9 and 831b9 located centromeric to the breakpoint (Romana et al, 1995a). These analyses showed: (1) an ETV6/CBFA2 fusion at both arms of the isochromosome, consequently re-interpreted as ider(21)(q10)t(12;21)(p12;q22); (2) a reciprocal fusion at the der(12)t(12;21); and (3) no signal at the del(12)(p12), neither by YAC nor cosmid probe...

show abstract

supporting

confidence: 53%

mentioning

confidence: 99%

Childhood acute lymphoblastic leukaemia with ider(21)(q10)t(12;21)(p12;q22): a new recurrent abnormality showing ETV6/CBFA2 fusion

Andreasson¹,

Johansson²,

Strömbeck³

et al. 1997

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…26 Using probes specific for the centromeric region and the long arm of the chromosome 6, we found that one case showed a pattern highly suggestive for the presence of an isochromosome 6p. This aberration is very common in human retinoblastoma, 27 but has also been reported in approximately 1% of acute lymphoblastic leukemia 28 and Hodgkin's lymphoma 29 and in 6% of primary mediastinal 30 and gastric NHLs, 25 as well as in individual cases of follicular, 10 nodal diffuse large B-cell 31 and nasal T/NK NHLs 32 and of Waldenstrom's macroglobulinemia. 33 It has been suggested that, similarly to cyclin D1 in mantle cell lymphoma and plasma cell myeloma, cyclin D3 may be deregulated in hematopoietic disorders as a consequence of the t(6;14) translocation.…”

Section: Discussionmentioning

confidence: 93%

Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

Pruneri

Valentini

Fabris

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

An abnormal expression of cyclin D3, a key regulator of the cell cycle, has been documented in a variety of human malignancies, and the cyclin D3 gene, mapping to 6p21, may be deregulated in plasma cell myeloma and non-Hodgkin's lymphoma as a result of the t(6;14)(p21.1;q32.3) translocation and/or gene amplification. In the current study, we for the first time investigated by immunohistochemistry and fluorescence in situ hybridization (FISH) the prevalence of cyclin D3 abnormalities in follicular lymphomas (FLs), comparing the results with traditional clinicopathologic characteristics, p27 and skp2 immunoreactivity (IR) and Ki-67 labeling index (LI). Cyclin D3, skp2 and Ki-67 IR significantly increased from grade I to grade III FL (p ‫؍‬ 0.0003, p ‫؍‬ 0.0001 and p < 0.0001, respectively), while p27 IR was significantly (p < 0.0001) more prevalent in low-grade tumors. Cyclin D3 IR was directly correlated with the Ki-67 LI (p < 0.0001) and inversely correlated with p27 IR (p ‫؍‬ 0.050). None of the 13 cases analyzed by FISH showed the t(6;14) translocation, but in 2 (15.3%) grade I FLs 3 cyclin D3 signals were detected. Cohybridization with probes specific for the centromeric region and the long arm of the chromosome 6 indicated trisomy in one case and a pattern highly suggestive for the presence of an isochromosome 6p in the other case. Our data suggest that the t(6;14) translocation may be extremely uncommon in FL and that a deregulated expression of cyclin D3, possibly due to epigenetic mechanisms, may be involved in the pathogenesis of high-grade tumors.

show abstract

“…Structural rearrangements involving duplication of the long arm of chromosome 21, dup (21), have also been described. [5][6][7][8][9][10][11][12][13][14] Fluorescence in situ hybridization (FISH) techniques showed that extra copies of the AML1 gene were present on these abnormal chromosomes. 6,[9][10][11][12][13][14] In one of two patients, for whom the amplified regions were shown to extend beyond the AML1 gene in both centromeric and telomeric directions, the amplification included the ERG and ETS2 genes.…”

Section: Introductionmentioning

confidence: 99%

Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases

et al. 2003

View full text Add to dashboard Cite

This study identifies multiple copies of the AML1 gene on a duplicated chromosome 21, dup(21), as a recurrent abnormality in acute lymphoblastic leukemia (ALL). Clusters of AML1 signals were visible at interphase by fluorescence in situ hybridization (FISH). In metaphase, they appeared tandemly duplicated on marker chromosomes of five distinct morphological types: large or small acrocentrics, metacentrics, submetacentrics or rings. The markers comprised only chromosome 21 material. Karyotypes were near-diploid and, besides dup(21), no other established chromosomal changes were observed. A total of 20 patients, 1.5 and o0.5% among consecutive series of childhood and adult ALL respectively, showed this phenomenon. Their median age was 9 years, white cell counts were low and all had a pre-B/common immunophenotype. Although this series is not the first report of this abnormality, it is the largest, permitting a detailed description of the variety of morphological forms that duplicated chromosome 21 can assume.

show abstract

Isochromosomes in acute lymphoblastic leukaemia: I(21q) is a significant finding

Cited by 32 publications

References 18 publications

Childhood acute lymphoblastic leukaemia with ider(21)(q10)t(12;21)(p12;q22): a new recurrent abnormality showing ETV6/CBFA2 fusion

Childhood acute lymphoblastic leukaemia with ider(21)(q10)t(12;21)(p12;q22): a new recurrent abnormality showing ETV6/CBFA2 fusion

Cyclin D3 immunoreactivity in follicular lymphoma is independent of the t(6;14)(p21.1;q32.3) translocation or cyclin D3 gene amplification and is correlated with histologic grade and Ki‐67 labeling index

Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases

Contact Info

Product

Resources

About