Characteristics of patients with TEL‐AML1‐positive acute lymphoblastic leukemia with single or multiple fusions

Al‐Sweedan, Suleimman; Neglia, Joseph P.; Steiner, Marie; Bostrom, Bruce; Casey, Timothy; Hirsch, Betsy A.

doi:10.1002/pbc.20911

Cited by 11 publications

(14 citation statements)

References 45 publications

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“…6 showed a unique FISH profile where two fusion signals of the ETV6/RUNX1 were detected. Double ETV6/RUNX1 fusion signals were found in 25% of ETV6/RUNX1 positive ALL patients [20]. Previous studies have found that the additional ETV6/RUNX1 fusion signal may have arisen from duplication of the der(21)t(12;21) chromosome [21,22], duplication of ETV6/RUNX1 fusion gene that was later translocated onto another chromosome [22] or ider(21)(q10)t(12;21)(p12;q22) [23].…”

Section: Discussionmentioning

confidence: 99%

Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization

et al. 2012

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BackgroundAcute lymphoblastic leukemia (ALL) is a heterogeneous form of hematological cancer consisting of various subtypes. We are interested to study the genetic aberration in precursor B-cell ALL with specific t(12;21) translocation in childhood ALL patients. A high resolution 244K array-based Comparative Genomic Hybridization (array-CGH) was used to study eleven ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL) patients.Result155 chromosomal aberrations (119 losses, 36 gains) were reported in the array findings, corresponding to 76.8% deletions and 23.2% amplifications. The ETV6 gene deletion occurred in 4 of the patients, corresponding to 45% of the sample. The most common alterations above 1 Mb were deletion 6q (13%), 12p (12%) and 9p (8%), and duplication 4q (6%) and Xq (4%). Other genes important in ALL were also identified in this study including RUNX1, CDKN2A, FHIT, and PAX5. The array-CGH technique was able to detect microdeletion as small as 400 bp.ConclusionThe results demonstrate the usefulness of high resolution array-CGH as a complementary tool in the investigation of ALL.

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Section: Discussionmentioning

confidence: 99%

Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization

et al. 2012

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“…19,24 Expression of CD13 occurs more often than CD33. 24 In our study, both CD13 and CD33 were more frequently expressed in the double ETV6-RUNX1 fusion group than the single-fusion group (Table 3) and were either absent or infrequently expressed in B-ALL with RUNX1 amplification.…”

Section: Discussionmentioning

confidence: 99%

“…24 In our study, both CD13 and CD33 were more frequently expressed in the double ETV6-RUNX1 fusion group than the single-fusion group (Table 3) and were either absent or infrequently expressed in B-ALL with RUNX1 amplification. 1,19 This suggests that the breakpoint of RUNX1 at 21q22 is myeloid associated when fused with other genes, as seen in AML with t(8;21)(q22;q22)/ RUNX1-RUNX1T1 or MDS with t(3;21)(q26;q22)/RUNX1-MECOM. [5][6][7] It also seems that the increased number of ETV6-RUNX1 fusions, rather than gain of the wild-type RUNX1, promotes more frequent expression of myeloidassociated antigens in malignant B-lymphoblasts.…”

Section: Discussionmentioning

confidence: 99%

“…The significance of these findings remains to be determined. 19,24 Several retrospective studies had conflicting results: some researchers in the past concluded that expression of myeloidassociated antigens was an independent, unfavorable prognostic indicator in ALL, 25,26 while recently others thought it was not significant. 27,28 With respect to the biologic behavior and outcome, the literature reports that patients with B-ALL with RUNX1 amplification usually have an increased risk of relapse and worse overall prognosis, and the patients should be considered high risk.…”

Section: Discussionmentioning

confidence: 99%

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Heterogeneity of Abnormal RUNX1 Leading to Clinicopathologic Variations in Childhood B-Lymphoblastic Leukemia

Knez

Carstens

Swisshelm

et al. 2015

American Journal of Clinical Pathology

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“…The most frequently observed translocations in the childhood ALL are t(12;21)(p13;q22) at a rate of 20-25 %; t(9;22)(q34;q11) at a rate of 2 %; and MLL gene rearrangement at a rate of 2-4 % (1, 2). It is stated that in these translocations t(12;21)(p13;q22) is related to good prognosis while t(9;22) (q34;q11) and MLL gene rearrangement are related to poor prognosis (10,11). Except these classic translocations, there are some rare translocations, which might affect prognosis in literature (6)(7)(8).…”

Section: Discussionmentioning

confidence: 99%

The variant translocation of ABL1 Gene t(2;9)(q21;q34) in a childhood T-cell acute lymphoblastic leukemia

Karkucak¹,

Yakut²,

Baytan³

et al. 2012

BLL

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Abstract:We present the case of the childhood ALL that was identifi ed by the translocation of the ABL1 gene to the q21 band of chromosome 2 without t(9;22)(q34;q11) translocation. The observation of a poor clinical course of the case may contribute to explanation of the action of t(9;22)(q34;q11) translocation, of which poor prognostic action is known on ALL's, in terms of ABL1 gene, independent of the BCR gene. On the other hand, the prognostic signifi cance of this variant ABL1 translocation detection, which is very rarely observed, will cast a light on future cases (Tab. 1, Fig. 1 Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, which accounts for one third of all pediatric cancers. Some numerical and structural chromosomal abnormalities, including the translocations t(9;22)(q34;q11), t(12;21) (p13;q22), rearrangements of the MLL gene, hyperdiploidy and hypodiploidy are known as prognostic factors in the childhood ALL. Hyperdiploidy is defi ned as the gain of one or more chromosomes in a nonrandom fashion. In older children with B-precursor ALL, the two most common chromosomal abnormalities are high hyperdiploid (51-65 chromosomes or DNA index ≥1.16) and the t(12;21)(p13;q22) translocation, each observed in approximately one-third of cases. Whereas t(9;22)(q34;q11), rearrangements of the MLL gene translocations and hypodiploidy are well known to be poor prognostic factors, the translocation of t(12;21)(p13;q22) and hyperdiploidy is speculatively a good prognostic marker(1-5). The Abelson tyrosine kinase gene (ABL1) is located on chromosomal band 9q34. The main fusion partner of ABL1 gene is BCR (Breakpoint Cluster Region), involved in the t(9;22)(q34;q11), present in more than 95 % of patients with chronic myeloid leukemia, in 20 % of adults with pre-B ALL and in 2-3 % of childhood ALL (6).Furthermore, it is known that the ABL1 gene rarely translocates to chromosomes 1q24,14q32 and 10q22.3 (6-8). In generally, some chromosomal abnormalities are not found at diagnosis, but may develop after treatment. We report a very rare variant of ABL1 translocation involved in a t(2;9)(q21;q34), which may cast a light on prognosis of similar cases in future. Case reportA two-year-old girl was hospitalized at our department of pediatric hematology in May 2007 with a compliant of a nodule in the neck. During the physical examination, multiple lymphadenopathy, hepatosplenomegaly and skin related symptoms were detected. Hematological data were as follows: hemoglobin level 8 g/dl, white blood cell level 324 x 10 9 /l with 100 % blast cells and platelets at a level of 57 x 10 9 /l. Bone marrow aspirate showed hypercellularity with 100 % of lymphoblasts. Immunophenotyping showed results corresponding to T-ALL. The ALL BFM-95 treatment protocol was started. On day 8, steroid response was poor. The bone marrow examination was performed on day 15 and concluded as hypocellular. On day 30 of the treatment, the leukocyte level running earlier at a range of 3 x 10 9 /l -5 x 10 9 /l was identifi ed to rise up ...

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Characteristics of patients with TEL‐AML1‐positive acute lymphoblastic leukemia with single or multiple fusions

Cited by 11 publications

References 45 publications

Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization

Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization

Heterogeneity of Abnormal RUNX1 Leading to Clinicopathologic Variations in Childhood B-Lymphoblastic Leukemia

The variant translocation of ABL1 Gene t(2;9)(q21;q34) in a childhood T-cell acute lymphoblastic leukemia

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