TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia

McLean, TW; Ringold, Sarah; Neuberg, Donna; Stegmaier, Kimberly; Tantravahi, Ramana; Ritz, Justin; Koeffler, H. Phillip; Takeuchi, Seisho; Janssen, J. W. G.; Seriu, Taku; Bartram, CR; Sallan, SE; Gilliland, D. Gary; Golub, Todd R.

doi:10.1182/blood.v88.11.4252.bloodjournal88114252

Cited by 245 publications

(102 citation statements)

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“…Of these t (12;21), the ETV6-RUNX1 fusion, the most commonly occurring translocation, is seen in 17-27% of childhood ALL and has been correlated with favorable outcomes. [24,25] Testing for ETV6-RUNX1 was introduced and used consistently at AKUH from May 2011; a few patients were tested intermittently at the other two institutions. Although only 53 patients with results could be analyzed, 13.2% were positive for this translocation possibly suggesting a slightly lower prevalence as compared to reported data.…”

Section: Discussionmentioning

confidence: 99%

Clinical features and induction outcome of childhood acute lymphoblastic leukemia in a lower/middle income population: A multi-institutional report from Pakistan

Fadoo

Nisar

Yousuf

et al. 2015

Pediatr Blood Cancer

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Background Acute lymphoblastic leukemia (ALL) is the most common cancer of childhood. Some evidence suggests differences in clinical and cytogenetic characteristics of ALL based on geographic and ethnic variations. However, data on ALL characteristics and early outcome of therapy from low/middle‐income countries such as Pakistan are scanty. Procedure A prospective, multi‐institutional cohort study in Karachi enrolled 646 newly diagnosed children with ALL over 3 years. Standard forms were used to collect demographic, clinical, and laboratory data at presentation and at the end of induction. Results Of the total, 66.1% (n = 427) were males. Median age was 6 (mean ± SE 6.87 ± 0.16; range 0.16–18) years. The most common clinical presentation was fever (88.7%). BPC‐ALL was diagnosed in 78.5%, while 17.5% had T‐ALL; 28.8% had a WBC >50 × 109/L. With 316 patients karyotyped, hypodiploidy and hyperdiploidy were seen in 5.1% and 10.7%, respectively. Of those tested, ETV6‐RUNX1 translocation was detected in 13.2%, while BCR‐ABL1 translocation and MLL gene rearrangements were seen in 7.3% and 4.6%, respectively. The cumulative loss to follow up before and during induction was 12.8% (n = 83) and 11.5% (n = 74) died before or during this phase. Induction was successfully completed by only 75.6% (n = 489) of the entire cohort and 69.6% (n = 450) achieved remission. Conclusion These patients had ALL with higher risk features than that reported from developed countries. One quarter failed to complete induction chemotherapy. This suboptimal result requires further study and development of innovative interventions, particularly focusing on the causes and solutions for late referral, abandonment, and infections. Pediatr Blood Cancer 2015;62:1700–1708. © 2015 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 99%

Clinical features and induction outcome of childhood acute lymphoblastic leukemia in a lower/middle income population: A multi-institutional report from Pakistan

Fadoo

Nisar

Yousuf

et al. 2015

Pediatr Blood Cancer

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“…Moreover, it was involved in t(10;12)(q24;p13) in a CMMoL patient and t(12;22)(p13;q11) in myeloproliferative disorders, resulting in the fusion of the TEL gene to the MN1 gene on 22q11 (Wlodarska et al, 1995;Buijs et al, 1995). TEL/AML-1 fusion resulting from a t(12;21)(p13;q22) translocation was observed in 16-27% of childhood ALL (Mclean et al, 1996). The frequent involvement of TEL in chromosomal translocations suggests that this gene plays an important role in the pathogenesis of human leukaemias.…”

Section: Discussionmentioning

confidence: 99%

Microsatellite instability and other molecular abnormalities in childhood acute lymphoblastic leukaemia

et al. 1997

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Microsatellite instability (MSI) has been considered to represent the defect of DNA mismatch repair systems and has been implicated in the tumourigenesis of several human malignancies. To investigate the possible presence of microsatellite instability in childhood acute lymphoblastic leukaemia (ALL), we examined 48 primary ALL samples. Instability was determined at 85 different microsatellite loci localized to 12 different chromosome arms. Microsatellite instability was detected in five (10%) samples. Interestingly, the instability was found at chromosomal regions associated with frequent alterations. Two samples had instability at the microsatellite marker within the TEL gene on chromosome arm 12p. Two other samples had instability at a microsatellite marker close to CDKN2/p16 on 9p; one of these samples had a homozygous deletion at 9p21. The fifth sample had instability at the microsatellite marker on 6q, which we have found is a frequent region of loss of heterozygosity in childhood ALL. Taken together, instability was rare in childhood ALL, but was localized to the three most frequently deleted chromosome regions in childhood ALL, suggesting that localized microsatellite instability may identify a fragile chromosomal region which could result in alteration of surrounding target genes and lead to leukaemia.

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“…A number of RT-PCR and FISH-based studies have shown t(12;21), to be the most common translocation in childhood ALL, occuring in 25-30% of B-lineage patients (4,30,(33)(34)(35)(36), although a much lower incidence (1-4.4%) has been described in adults (32,(37)(38)(39).…”

Section: T(12;21)(p13;q22)mentioning

confidence: 99%

The Leukaemia Research Fund/United Kingdom Cancer Cytogenetics Group Karyotype Database in acute lymphoblastic leukaemia: a valuable resource for patient management

Harrison¹,

Martineau²,

Secker-Walker

2001

Br J Haematol

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TEL/AML-1 dimerizes and is associated with a favorable outcome in childhood acute lymphoblastic leukemia

Cited by 245 publications

References 0 publications

Clinical features and induction outcome of childhood acute lymphoblastic leukemia in a lower/middle income population: A multi-institutional report from Pakistan

Clinical features and induction outcome of childhood acute lymphoblastic leukemia in a lower/middle income population: A multi-institutional report from Pakistan

Microsatellite instability and other molecular abnormalities in childhood acute lymphoblastic leukaemia

The Leukaemia Research Fund/United Kingdom Cancer Cytogenetics Group Karyotype Database in acute lymphoblastic leukaemia: a valuable resource for patient management

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