Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia

Lee, Shawn H. R.; Antillón‐Klussmann, Federico; Pei, Deqing; Yang, Wenjian; Roberts, Kathryn G.; Li, Zhenhua; Devidas, Meenakshi; Yang, Wentao; Najera, Cesar; Lin, Hai; Tan, Ah Moy; Ariffin, Hany; Cheng, Cheng; Evans, William E.; Hunger, Stephen P.; Jeha, Sima; Mullighan, Charles G.; Loh, Mignon L.; Yeoh, Allen Eng Juh; Pui, Ching‐Hon; Yang, Jun J.

doi:10.1001/jamaoncol.2021.6826

Cited by 49 publications

(56 citation statements)

References 44 publications

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“…This finding is consistent with a recent study showing that patients with African, Native American and East Asian genetic ancestry have higher proportion of this genotype as compared to those with European ancestry among whom approximately 3% of the patients have this genotype. 8 Our study yielded a 5-year event-free survival of 84.4% (95% CI, 80.6-88.3) and 5year overall survival of 88.9% (95% CI, 85.5-92.4), results consistent with those of other clinical trials conducted after 2000 (Supplemental Table 4). The recent improvement in outcome was largely due to the use of more refined risk-adapted treatment including measurement of MRD.…”

Section: Discussionsupporting

confidence: 89%

“…Contemporary therapies have yielded 5-year event-free survival and overall survival rates exceeding 80% and 90%, respectively, for childhood acute lymphoblastic leukemia (ALL) [1][2][3][4]. TCF3-PBX1, resulting from the t(1;19) (q23;p13), is one of the most frequent genetic abnormalities, affecting 3% to 12% of pediatric B-ALL cases, depending on the genetic ancestry [1,[5][6][7][8]. This genotype had historically been associated with a poor prognosis [9][10][11] and increased central nervous system (CNS) relapse [12].…”

Section: Introductionmentioning

confidence: 99%

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Prognostic factors of childhood acute lymphoblastic leukemia with TCF3-PBX1 in CCCG-ALL-2015: a multi-center study

Zhang

Wan

Wang

et al. 2022

Preprint

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To identify prognostic factors that can be used to further improve outcome, we studied 384 patients with this genotype treated on Chinese Children’s Cancer Group acute lymphoblastic leukemia (ALL) -2015 protocol between 1 January 2015 and 31 December 2019. All patients provisionally received intensified chemotherapy in the intermediate-risk. The overall 5-year event-free survival (EFS) was 84.4% (95% confidence interval [CI], 80.6-88.3). Independent factors associated with lower 5-year EFS were male sex (80.4%, [95% CI, 74.8-86.4] vs. 88.9%, [95% CI, 84.1-93.9] in female, p = 0.033) and positive Day 46 minimal residual disease (MRD) (≥ 0.01%) (62.1%, [95% CI, 44.2-87.4] vs. 87.1%, [95% CI, 83.4-90.9] in patients with negative MRD, p < 0.001). The presence of testicular leukemia at diagnosis (n=10) was associated with particularly poorer 5-year EFS (33.3% [95% CI, 11.6-96.1] vs. 83.0% [95% CI, 77.5-88.9] in the other 192 male patients, P < 0.001) and was an independent risk factor (HR, 5.7, [95% CI, 2.2-14.5], p < 0.001). These data suggest that the presence of positive MRD after intensive remission induction and testicular leukemia at diagnosis are indications for new molecular therapeutics or immunotherapy in patients with TCF3-PBX1 ALL.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Prognostic factors of childhood acute lymphoblastic leukemia with TCF3-PBX1 in CCCG-ALL-2015: a multi-center study

Zhang

Wan

Wang

et al. 2022

Preprint

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“…In this regard, it has been described that when the Amerindian (indigenous) ancestry is higher, the ETV6-RUNX1 is less common. This type of ancestry has been consistently associated with a high incidence and poor prognosis of childhood ALL and in a recent study was reported that the Amerindian is the most prevalent ancestry in pediatric population of MC ( 148 , 149 ). Until date, the reasons behind this relationship has not been established and further investigation is required for explaining the high incidence and mortality rates observed in Hispanic populations ( 150 ).…”

Section: Discussionmentioning

confidence: 95%

Persistently high incidence rates of childhood acute leukemias from 2010 to 2017 in Mexico City: A population study from the MIGICCL

Flores-Lujano

Duarte-Rodríguez

Jiménez‐Hernández

et al. 2022

Front. Public Health

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IntroductionOver the years, the Hispanic population living in the United States has consistently shown high incidence rates of childhood acute leukemias (AL). Similarly, high AL incidence was previously observed in Mexico City (MC). Here, we estimated the AL incidence rates among children under 15 years of age in MC during the period 2010–2017.MethodsThe Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia conducted a study gathering clinical and epidemiological information regarding children newly diagnosed with AL at public health institutions of MC. Crude age incidence rates (cAIR) were obtained. Age-standardized incidence rates worldwide (ASIRw) and by municipalities (ASIRm) were calculated by the direct and indirect methods, respectively. These were reported per million population <15 years of age; stratified by age group, sex, AL subtypes, immunophenotype and gene rearrangements.ResultsA total of 903 AL cases were registered. The ASIRw was 63.3 (cases per million) for AL, 53.1 for acute lymphoblastic leukemia (ALL), and 9.4 for acute myeloblastic leukemia. The highest cAIR for AL was observed in the age group between 1 and 4 years (male: 102.34 and female: 82.73). By immunophenotype, the ASIRw was 47.3 for B-cell and 3.7 for T-cell. The incidence did not show any significant trends during the study period. The ASIRm for ALL were 68.6, 66.6 and 62.8 at Iztacalco, Venustiano Carranza and Benito Juárez, respectively, whereas, other municipalities exhibited null values mainly for AML.ConclusionThe ASIRw for childhood AL in MC is among the highest reported worldwide. We observed spatial heterogeneity of rates by municipalities. The elevated AL incidence observed in Mexican children may be explained by a combination of genetic background and exposure to environmental risk factors.

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“…In the same context, it has been observed that the incidence of ALL subtypes and genetic susceptibility to ALL varies according to geographic regions and ancestry of populations. Recently, it has been reported that in a population with a higher prevalence of Native American ancestry, the ETV6::RUNX1 fusion gene is found with lower frequency, and this population was associated with poor prognosis ( 29 ). This directly correlates with the ancestry analysis that was performed in Mexican ALL patients using AIMs (Ancestry-informative marker, single nucleotide polymorphism of frequency differences between populations) which showed that they belong to the mestizo group, enriched mainly by a Native American ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population

et al. 2022

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ETV6::RUNX1 is a genetic rearrangement of good prognosis in children with acute lymphoblastic leukemia (ALL). In Mexico, its prevalence is low in comparison with Caucasian populations. We developed a novel TaqMan one-step RT-qPCR approach to assess the prevalence of four genetic rearrangements in a cohort of Hispanic children with ALL from Mexico City. The prevalence of common fusion gene transcripts was as follows: TCF3::PBX1 7.7%; BCR::ABL1p190 3.3%; and KMT2A::AFF1 2.8%, and ETV6::RUNX1was observed with low prevalence (10.5%) in comparison to that reported for developed countries. This is consistent with previous findings on Mexican children with ALL and similar to those reported on children from Hispanic populations. The confirmation of a low prevalence of ETV6::RUNX1 in children of a Hispanic origin represents an advancement in the description of genetic factors of ALL in these populations.

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Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia

Cited by 49 publications

References 44 publications

Prognostic factors of childhood acute lymphoblastic leukemia with TCF3-PBX1 in CCCG-ALL-2015: a multi-center study

Prognostic factors of childhood acute lymphoblastic leukemia with TCF3-PBX1 in CCCG-ALL-2015: a multi-center study

Persistently high incidence rates of childhood acute leukemias from 2010 to 2017 in Mexico City: A population study from the MIGICCL

Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population

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