The presence of TEL/AML1 rearrangement and cryptic deletion of the TEL gene in adult acute lymphoblastic leukemia (ALL)

Lee, Dong Hoon; Kim, Young Ree; Cho, Hyung Kyun; Lee, Chung Kee; Lee, Jee Hyung; Cho, Han Ik

doi:10.1016/j.cancergencyto.2005.02.020

Cited by 12 publications

(4 citation statements)

References 5 publications

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“…Deletions in 9p21.3 targeting CDKN2A are well known in adult ALLs (9,23), although the high occurrence of homozygous deletions (17 of 21 cases with 9p21 loss; 81%) has not been previously reported. As regards ETV6, a recent FISH study reported ETV6 deletions in 3 of 74 (4%) of adult patients (24), which is substantially lower than the 18% detected among our cases, suggesting that SNP array analysis is in some instances superior to FISH for detection of small deletions. Deletions of PAX5, IKZF1, RB1, EBF1, or LEF1 have previously only been reported in single cases of adult ALL, but studies of pediatric cases have shown frequent loss (16,17).…”

Section: Discussioncontrasting

confidence: 71%

Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease

Paulsson

Cazier

MacDougall

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

100

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We present here a genome-wide map of abnormalities found in diagnostic samples from 45 adults and adolescents with acute lymphoblastic leukemia (ALL). A 500K SNP array analysis uncovered frequent genetic abnormalities, with cryptic deletions constituting half of the detected changes, implying that microdeletions are a characteristic feature of this malignancy. Importantly, the pattern of deletions resembled that recently reported in pediatric ALL, suggesting that adult, adolescent, and childhood cases may be more similar on the genetic level than previously thought. Thus, 70% of the cases displayed deletion of one or more of the CDKN2A, PAX5, IKZF1, ETV6, RB1, and EBF1 genes. Furthermore, several genes not previously implicated in the pathogenesis of ALL were identified as possible recurrent targets of deletion. In total, the SNP array analysis identified 367 genetic abnormalities not corresponding to known copy number polymorphisms, with all but two cases (96%) displaying at least one cryptic change. The resolution level of this SNP array study is the highest used to date to investigate a malignant hematologic disorder. Our findings provide insights into the leukemogenic process and may be clinically important in adult and adolescent ALL. Most importantly, we report that microdeletions of key genes appear to be a common, characteristic feature of ALL that is shared among different clinical, morphological, and cytogenetic subgroups. A cute lymphoblastic leukemia (ALL) occurs at all ages but displays a bimodal distribution of incidence, with one peak in early childhood and a second in patients older than 50 years (1). For adult ALL, the yearly incidence is Ϸ2 per 100,000, with Ϸ75% of the cases being B lineage and the remainder of T cell origin (1, 2). The most prominent prognostic factors are age, white blood cell count (WCC), and different genetic abnormalities, with younger age and lower WCC being associated with an improved outcome (3, 4). Most adults, however, are considered to be high-risk, and the long-term disease-free survival rates are Ͻ40% (1, 3-5). This is in stark contrast to pediatric ALL, where refined treatment regimens have resulted in cure rates approaching 80% (6, 7). Treatment of adolescents (15-21 years old) on pediatric protocols has resulted in an increased overall survival but is still far from the outstanding results achieved in children (8). Hence, there is a need for novel prognostic markers in adult and adolescent ALL to allow a better risk stratification of these patients and to identify new treatment targets.Whereas genetic abnormalities in pediatric ALL are widely used in clinical practice for risk stratification purposes, most treatment protocols in adult ALL consider only the presence or absence of the Philadelphia chromosome, t(9;22)(q34;q11.2). The t(9;22), which results in the BCR/ABL1 fusion gene, is found in 20-30% of adult B cell precursor cases and is an adverse prognostic indicator (9-12). Other recurrent rearrangements include the t(4;11)(q21;q23) forming a MLL/AFF1 (prev...

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Section: Discussioncontrasting

confidence: 71%

Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease

Paulsson

Cazier

MacDougall

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

100

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“…The TEL deletion without TEL/AML1 fusion has been reported rarely. Lee et al showed the cryptic deletion of TEL gene in the absence of TEL/AML1 rearrangement in three adult ALL patients (4.0 %) [28]. To clearly identify the incidence and significance of this abnormality, much more study is needed.…”

Section: Discussionmentioning

confidence: 95%

Evaluation of ETV6/RUNX1 Fusion and Additional Abnormalities Involving ETV6 and/or RUNX1 Genes Using FISH Technique in Patients with Childhood Acute Lymphoblastic Leukemia

Aydın

Çetin

Manguoğlu

et al. 2015

Indian J Hematol Blood Transfus

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Childhood acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia. Specifically, ALL is a malignant disorder of the lymphoid progenitor cells, with a peak incidence among children aged 2-5 years. The t(12;21)(p13;q22) translocation occurs in 25 % of childhood B cell precursor ALL. In this study, bone marrow samples were obtained from 165 patients with childhood ALL. We analyzed the t(12;21) translocation and other related abnormalities using the fluorescent in situ hybridization (FISH) technique with the ETV6(TEL)/RUNX1(AML1) ES dual color translocation probe. Conventional cytogenetic analyses were also performed. ETV6 and RUNX1 related chromosomal abnormalities were found in 42 (25.5 %) of the 165 patients with childhood ALL. Among these 42 patients, structural changes were detected in 33 (78.6 %) and numerical abnormalities in 9 (21.4 %). The frequency of FISH abnormalities in pediatric ALL cases were as follows: 8.5 % for t(12;21)(p13;q22) ETV6/RUNX1 fusion, 6.0 % for RUNX1 amplification, 3.0 % for tetrasomy/trisomy 21, 1.8 % for ETV6 deletion, 1.21 % for ETV6 deletion with RUNX1 amplification, 1.21 % for ETV6 amplification with RUNX1 amplification, 0.6 % for polyploidy, 0.6 % for RUNX1 deletion, and 0.6 % for diminished ETV6 signal. The most common structural abnormality was the t(12;21) translocation, followed by RUNX1 amplification and ETV6 deletion, while the most commonly observed numerical abnormality was trisomy 21.

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“…In particular, FISH is a useful tool for the detection of secondary aberrations as well as ETV6/RUNX1 rearrangement. Secondary aberrations in ETV6/RUNX1 rearrangement-positive B-ALL are deletion of the untranslocated ETV6 allele, gain of the second RUNX1 allele and duplication of the derivative chromosome 21 [1,2,3]. Here, we report a case of B-ALL with ETV6/RUNX1 rearrangement by RT-PCR, but lacking evidence of ETV6/RUNX1 rearrangement by FISH.…”

Section: Figmentioning

confidence: 93%

“…The frequency of ETV6 deletion in ETV6/RUNX1 rearrangement-positive B-ALL is 52-70% [2,3,5,6,7,8,9]. The ETV6 deletion in the absence of ETV6/RUNX1 rearrangement has been reported in 4% of adult ALL patients [1] and 18% of child ALL at relapse [2]. Without RT-PCR, our case might be mistakenly considered as a negative ETV6/RUNX1 rearrangement result having ETV6 deletion.…”

Section: Figmentioning

confidence: 99%

<b><i>ETV6/RUNX1</i></b> Rearrangement Identified by RT-PCR without Evidence on FISH

Hahm

Han

Mun³

et al. 2014

Acta Haematol

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The presence of TEL/AML1 rearrangement and cryptic deletion of the TEL gene in adult acute lymphoblastic leukemia (ALL)

Cited by 12 publications

References 5 publications

Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease

Microdeletions are a general feature of adult and adolescent acute lymphoblastic leukemia: Unexpected similarities with pediatric disease

Evaluation of ETV6/RUNX1 Fusion and Additional Abnormalities Involving ETV6 and/or RUNX1 Genes Using FISH Technique in Patients with Childhood Acute Lymphoblastic Leukemia

<b><i>ETV6/RUNX1</i></b> Rearrangement Identified by RT-PCR without Evidence on FISH

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