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

Abstract

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).

Quantitative multiparametric immunophenotyping in acute lymphoblastic leukemia: correlation with specific genotype. I. ETV6/AML1 ALLs identification

“…Accordingly, we show that the presence of these six phenotypic characteristics in childhood precursor B-ALL blast cells is specific (100%) for the t(12;21) translocation, although there is a small group of these patients (three, 14%) in which one or two of the six criteria listed above is lacking; in 2/3 of them additional cytogenetic abnormalities were found. This association between t(12;21) and abnormal karyotypes has been recently reported by Raynaud et al 53 In the present study we conclude that this multiparametric quantitative immunophenotyping approach seems to be able to identify homogeneous groups of ALLs also corresponding to genotypically determined types such as t(12;21) and also t(4;11) and hyperdiploid cases (De Zen manuscript in preparation). Our results enhanced the two properties reported in the Borowitz study: that an accurate phenotypic prediction of cytogenetic and molecular genetic abnormalities could not be obtained by either positive or negative antigen definition; only a more accurate description of the antigen expression pattern was able to demonstrate significant predictability.…”

Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia

“…93 The cytogenetically detectable 12p aberrations represent deletions, dicentric and (unbalanced) translocations. 93 In 72% of cases with t(12;21), the wild-type ETV6 gene on the second allele is lost.…”

“…93 The cytogenetically detectable 12p aberrations represent deletions, dicentric and (unbalanced) translocations. 93 In 72% of cases with t(12;21), the wild-type ETV6 gene on the second allele is lost. 93 Loss of heterozygosity studies even report higher frequencies of loss of the nontranslocated ETV6 allele, which is assumed to contribute to the oncogenic process as wild-type ETV6 might interfere with the oncogenic properties of the ETV6-containing fusion proteins.…”

“…93 In 72% of cases with t(12;21), the wild-type ETV6 gene on the second allele is lost. 93 Loss of heterozygosity studies even report higher frequencies of loss of the nontranslocated ETV6 allele, which is assumed to contribute to the oncogenic process as wild-type ETV6 might interfere with the oncogenic properties of the ETV6-containing fusion proteins. 94,95 Recently, it was shown that loss of ETV6 expression is a critical secondary event for leukomogenesis in ALL with a t(12;21)(p13;q22).…”

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

“…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.…”