Trisomy 21 is a recurrent secondary aberration in childhood acute lymphoblastic leukemia withTEL/AML1 gene fusion

Lončarević, Ivan F.; Roitzheim, Barbara; Ritterbach, J.; Viehmann, Susanne; Borkhardt, Arndt; Lampert, F.; Harbott, Jochen

doi:10.1002/(sici)1098-2264(199903)24:3<272::aid-gcc13>3.0.co;2-u

Cited by 59 publications

(51 citation statements)

References 28 publications

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“…It was therefore surprising that previous studies reported a significantly lower incidence of TEL/AML1 þ leukemia in these patients. 12,26,47 However, this is not the case in our cohort of patients, because two of the eight Down syndrome patients analyzed had a TEL/AML1 rearrangement, which concords with the expected overall frequency of this specific abnormality in childhood ALL.…”

Section: Patient Diagnosis Relapsementioning

confidence: 43%

“…26 The possibility to differentiate clearly between these two markers with FISH, together with the prospect to evaluate their distribution and incidence also in interphase cells, drastically improves their detection rate. 12,27 We found that in contrast to the subclones with a TEL deletion, the proportion of TEL/ AML1 þ cells with an extra chromosome 21 and duplicated der(21) was comparatively smaller.…”

Section: Patient Diagnosis Relapsementioning

confidence: 99%

“…Some of these events could be reflected on the chromosomal level as nonrandom secondary abnormalities and comprise, in particular, the deletion of the nonrearranged TEL allele, the duplications of the normal chromosome 21 and the der(21)t(12;21) as well as more unspecific ones such as 6q deletions and 9p abnormalities. [21][22][23][24][25][26][27][28][29][30][31][32] Since the t(12;21) is virtually undetectable with conventional cytogenetic procedures, the two preferred screening methods are those with reverse transcriptase polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH). 1-6, 9-13,17,21-33 The latter technology has the advantage that it enables the identification and quantification of the most common and, thus, most relevant secondary changes on a single cell level.…”

Section: Introductionmentioning

confidence: 99%

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Incidence and relevance of secondary chromosome abnormalities in childhood TEL/AML1+ acute lymphoblastic leukemia: an interphase FISH analysis

Attarbaschi

Mann

König³

et al. 2004

Leukemia

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The aim of the present study was to determine the frequency and clinical relevance of the most common secondary karyotype abnormalities in TEL/AML1 þ B-cell precursor acute lymphoblastic leukemia (ALL) as assessed with fluorescence in situ hybridization (FISH) analyses. Screening of 372 patients who were enrolled in two consecutive Austrian childhood ALL multicenter trials identified 94 (25%) TEL/AML1 þ cases. TEL deletions, trisomy 21 and an additional der(21)t(12;21) were detected in 52 (55%), 13 (14%) and 14 (15%) TEL/AML1 þ patients, respectively. The 12p aberrations (P ¼ 0.001) and near tetraploidy (P ¼ 0.045) were more common in TEL/AML1 þ patients, whereas the incidence of diploidy, pseudodiploidy, hypodiploidy, low hyperdiploidy, near triploidy, del(6q), chromosome 9 and 11q23 abnormalities was similar among TEL/ AML1 þ and TEL/AML1À patients. None of the TEL/AML1 þ patients had a high hyperdiploid karyotype. Univariate analysis indicated that among TEL/AML1 þ patients those with a deletion of the nontranslocated TEL allele had a worse prognosis than those without this abnormality (P ¼ 0.034). We concluded that the type and incidence of the most common secondary aberrations in TEL/AML1 þ ALL can be conveniently identified with little additional effort during interphase screening with appropriate TEL and AML1 FISH probes. We also provided preliminary evidence that the deletion of the nontranslocated TEL allele may adversely influence the clinical course of TEL/AML1 þ ALL.

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Section: Patient Diagnosis Relapsementioning

confidence: 43%

Section: Patient Diagnosis Relapsementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Incidence and relevance of secondary chromosome abnormalities in childhood TEL/AML1+ acute lymphoblastic leukemia: an interphase FISH analysis

Attarbaschi

Mann

König³

et al. 2004

Leukemia

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“…Interestingly, the ETV6 gene has been shown to be fused to the homeobox gene CDX2 in a patient with acute myeloid leukemia and a t(12;13)(p13;q12), 28 and a preliminary study by Coignet et al 29 suggests that myeloid-and lymphoid-specific breakpoint cluster regions are present within chromosome 13q14 in patients with acute leukemia and with a t(12;13)(p12;q12-14).…”

Section: Discussionmentioning

confidence: 99%

Cytogenetic abnormalities associated with the t(12;21): a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia

Raynaud¹,

Dastugue²,

Zoccola³

et al. 1999

Leukemia

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The t(12;21)(p13;q22) is a cryptic abnormality observed in 25% of children with B-lineage acute lymphoblastic leukemia (ALL), associated with a favorable prognosis. To determine whether specific cytogenetic abnormalities accompany the t(12;21), we analyzed the cytogenetic profiles of blast cells from 169 ALL cases positive for the t(12;21), previously identified by molecular methods. Only 13.6% of samples had normal karyotypes. Structural changes were detected in 89.7% of abnormal karyotypes, and numerical abnormalities in 47%. Rearrangements of 12p were the most frequent structural aberration (57 out of 146 patients with chromosomal abnormalities). Nonspecific deletions of chromosomes 6 and 9 were also found. The most frequent numerical abnormalities was trisomy for chromosomes 21. Blast cells were pseudodiploid (45.6%), hyperdiploid with 47 to 51 chromosomes (24.3%), hypodiploid with 44 to 45 chromosomes (10%), near-triploid (0.6%), or near-tetraploid (5.9%). Our results show that the t(12;21) is not associated with hyperdiploidy of 52 to 68 chromosomes or with the prognostic t(1;19), t(4;11) or t(9;22). Only children with B-lineage ALL who lack these abnormalities detected by conventional cytogenetics will probably benefit from additional testing by molecular methods to detect the t(12;21).

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“…11,12 Trisomy 21 and duplication of the der(21)t(12;21) are also found in t(12;21)-positive patients, with the latter apparently being more common in relapsed cases. [13][14][15][16] However, the number of patients screened in these studies is limited. The prognostic significance of additional genetic abnormalities in TEL and AML1 is therefore unknown.…”

Section: Introductionmentioning

confidence: 99%

Incidence of additional genetic changes in the TEL and AML1 genes in DCOG and COALL-treated t(12;21)-positive pediatric ALL, and their relation with drug sensitivity and clinical outcome

et al. 2006

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Clinical heterogeneity within t(12;21) or TEL/AML1-positive ALL (25% of childhood common/preB ALL) indicates that additional genetic changes might contribute to outcome. We studied the relation between additional genetic changes in TEL(ETV6) and AML1(RUNX1) (FISH), drug sensitivity (MTT assay) and clinical outcome in 143 DCOG and COALL-treated t(12;21)-positive ALL patients. Additional genetic changes in TEL and AML1 were present in 83% of the patients, and consisted of (partial) deletion of the second TEL gene (70%), an extra AML1 gene (23%) or an extra der(21)t(12;21) (10%). More than one additional change was observed in 20%. Disease-free survival (pDFS) of DCOG patients without additional genetic changes (4 years pDFS7s.e. 53717%) and of those with an extra der(21)t(12;21) (60722%) is poorer than that of compared to patients with other additional genetic changes in TEL or AML1 (7976%; P-trend ¼ 0.02). This was mainly due to the occurrence of early relapses within 2.5 years after the first diagnosis. Similar observations were found in the COALL cohort, albeit not significant owing to limited follow-up. Multivariate analysis including age, WBC and genetic abnormalities in TEL and/or AML1 showed that especially, in vitro resistance to prednisolone (hazard ratio 5.78, 95% CI 1.45-23.0; P ¼ 0.01) is an independent prognostic factor in DCOG-and COALL-treated t(12;21)-positive ALL.

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Trisomy 21 is a recurrent secondary aberration in childhood acute lymphoblastic leukemia withTEL/AML1 gene fusion

Cited by 59 publications

References 28 publications

Incidence and relevance of secondary chromosome abnormalities in childhood TEL/AML1+ acute lymphoblastic leukemia: an interphase FISH analysis

Incidence and relevance of secondary chromosome abnormalities in childhood TEL/AML1+ acute lymphoblastic leukemia: an interphase FISH analysis

Cytogenetic abnormalities associated with the t(12;21): a collaborative study of 169 children with t(12;21)-positive acute lymphoblastic leukemia

Incidence of additional genetic changes in the TEL and AML1 genes in DCOG and COALL-treated t(12;21)-positive pediatric ALL, and their relation with drug sensitivity and clinical outcome

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