Genetic variants and clinical significance of pediatric acute lymphoblastic leukemia

Zhang, Honghong; Wang, Hongsheng; Qian, Xiaowen; Fan, Cuiqing; Li, Jun; Miao, Hui; Zhu, Xiaohua; Yu, Yi; Meng, Jianhua; Cao, Ping; Le, Jie; Jiang, Junye; Jiang, Wen-Jing; Wang, Ping; Zhai, Xiaowen

doi:10.21037/atm.2019.04.80

Cited by 20 publications

(17 citation statements)

References 39 publications

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“…Regarding immune-phenotyping of examined hematologic cancers, it was found that majority of ALL were of B-lineage (84.6%) which is similar to the observations of Zhang et al, 2019, (29) who found that 81.4% were B-cell ALL. The patients with AML mainly had M1-M2 type (38.1%), followed by M4-M5 type (26.2%) which is similar to the findings of Noronha et al, 2011, who found that the most common types of AML were M4 followed by M1 (33.4% and 22.2%, respectively).…”

Section: Discussionsupporting

confidence: 85%

Pattern and Survival of Childhood Malignancies: A 10-Year Retrospective Study

Manzour¹,

Makkeyah²,

Shawiesh³

et al. 2021

Journal of High Institute of Public Health

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Background: Hematopoietic neoplasms constitute more than 40% of malignancies in children and represent a wide range of disorders, including acute leukemias and lymphomas. Childhood cancer is curable if diagnosed early, and the survival has improved dramatically over the last 20 years due to aggressive combined modality management. Objective: To estimate the proportion of hematologic malignancies, identify patient characteristics, and calculate the overall and event-free survival of childhood malignancies at the Pediatric Oncology Clinic, Ain Shams University Hospital. Methods: A total of 220 patients with acute lymphoblastic leukemia (ALL), 42 patients with acute myeloid leukemia (AML), 65 patients with non-Hodgkin lymphoma (NHL), and 29 patients with Hodgkin's lymphoma (HL), registered at the Pediatric Oncology Clinic, Ain Shams University Children's Hospital from January 2005 through December 2014, were included in the study. A checklist adapted from patients' files contents was filled, and overall survival (OS) and event-free survival (EFS) were studied. Results: The most common type of hematologic malignancies among children was ALL (61.8%). Regarding patients with ALL, the mean age at diagnosis was 6.1 ± 3.9 years, and the male : female ratio was 1.2:1. The 10-year OS was 85.3%, and the 10-year EFS was 80.4%. In the AML group, the OS was 78.8%, and the EFS was 74.4%. The OS and EFS of the patients with NHL were 89.1% and 84.6%, respectively. The 10-year OS and EFS for patients with HL were 88.9% and 75.9%, respectively. Conclusion:The survival rates of ALL, AML, and NHL approach universal estimates. The survival rates of patients with HL was lower than international rates, which mandates the application of response-based therapy. The high survival rates of patients with AML was attributed to the definition of risk groups, which led to a more risk-adapted treatment.

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Section: Discussionsupporting

confidence: 85%

Pattern and Survival of Childhood Malignancies: A 10-Year Retrospective Study

Manzour¹,

Makkeyah²,

Shawiesh³

et al. 2021

Journal of High Institute of Public Health

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“…Furthermore, ALL patients carrying mutations in NOTCH1 and PTEN presented signi cantly high initial WBC counts. Combined with the data of previous studies, a signi cant correlation was established between higher initial WBC counts and T-ALL compared to B-ALL(Zhang et al 2019). In addition, patients with FLT3 mutations showed lower platelet counts and hemoglobin levels, while patients with NOTCH1 mutations had higher hemoglobin levels.…”

supporting

confidence: 57%

Spectrum and Clinical Characteristics of Gene Mutations in Chinese Pediatric Acute Lymphoblastic Leukemia

Shen

Liu

et al. 2021

Preprint

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Purpose The 5-year survival rate of children with acute lymphoblastic leukemia (ALL) is 85–90%, with a 10–15% rate of treatment failure. Next-generation sequencing (NGS) identified recurrent mutated genes in ALL that might alter the diagnosis, classification, prognostic stratification, treatment, and response to ALL. Few studies on gene mutations in Chinese pediatric ALL have been identified. Thus, an in-depth understanding of the biological characteristics of these patients is essential.. The present study aimed to characterize the spectrum and clinical features of recurrent driver gene mutations in a single-center cohort of Chinese pediatric ALL. Methods We enrolled 219 patients with pediatric ALL in our single center. Targeted sequencing based on NGS was used to detect gene mutations in patients. The correlation was analyzed between gene mutation and clinical features, including patient characteristics, cytogenetics, genetic subtypes, risk stratification and treatment outcomes using χ2-square test or Fisher’s exact test for categorical variables. Results A total of 381 gene mutations were identified in 66 different genes in 152/219 patients. PIK3R1 mutation was more common in infants (p = 0.021). KRAS and FLT3 mutations were both more enriched in patients with hyperdiploidy (P < 0.0001, P = 0.0003, respectively). NRAS, PTPN11, FLT3, and KMT2D mutations were more common in patients who did not carry the fusion genes (all p < 0.05). PTEN mutation was significantly associated with high-risk ALL patients (P = 0.011), while NOTCH1 mutation was common in middle-risk ALL patients (P = 0.039). Patients with ETV6 or PHF6 mutations were more sensitive to steroid treatment (P = 0.033, P = 0.048, respectively). Conclusion This study depicted the specific genomic landscape of Chinese pediatric ALL and revealed the relevance between mutational spectrum and clinical features of Chinese pediatric ALL, which highlights the need for molecular classification, risk stratification, and prognosis evaluation.

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“…The PHF6 locus is one of the most frequently mutated genes in T-lymphoblastic leukemia (T-ALL). Inactivating mutations of PHF6 have been identified in 5-16% of pediatric and 19-40% of adult patients with T-ALL and~25% of adults with Tlymphoblastic lymphoma (T-LBL) with some groups identifying an association with NOTCH1 mutations (67%-84.6% of PHF6 mutated/deleted T-ALL with NOTCH1 mutations versus 39.8% PHF6 WT) (4,(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Copy number alterations of PHF6 in pediatric T-ALL has been reported to be between 13-14% (39,40).…”

Section: T-lymphoblastic Leukemiamentioning

confidence: 99%

PHF6 Mutations in Hematologic Malignancies

Kurzer

Weinberg

2021

Front. Oncol.

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Next generation sequencing has uncovered several genes with associated mutations in hematologic malignancies that can serve as potential biomarkers of disease. Keeping abreast of these genes is therefore of paramount importance in the field of hematology. This review focuses on PHF6, a highly conserved epigenetic transcriptional regulator that is important for neurodevelopment and hematopoiesis. PHF6 serves as a tumor suppressor protein, with PHF6 mutations and deletions often implicated in the development of T-lymphoblastic leukemia and less frequently in acute myeloid leukemia and other myeloid neoplasms. PHF6 inactivation appears to be an early event in T-lymphoblastic leukemogenesis, requiring cooperating events, including NOTCH1 mutations or overexpression of TLX1 and TLX3 for full disease development. In contrast, PHF6 mutations tend to occur later in myeloid malignancies, are frequently accompanied by RUNX1 mutations, and are often associated with disease progression. Moreover, PHF6 appears to play a role in lineage plasticity within hematopoietic malignancies, with PHF6 mutations commonly present in mixed phenotype acute leukemias with a predilection for T-lineage marker expression. Due to conflicting data, the prognostic significance of PHF6 mutations remains unclear, with a subset of studies showing no significant difference in outcomes compared to malignancies with wild-type PHF6, and other studies showing inferior outcomes in certain patients with mutated PHF6. Future studies are necessary to elucidate the role PHF6 plays in development of T-lymphoblastic leukemia, progression of myeloid malignancies, and its overall prognostic significance in hematopoietic neoplasms.

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Genetic variants and clinical significance of pediatric acute lymphoblastic leukemia

Cited by 20 publications

References 39 publications

Pattern and Survival of Childhood Malignancies: A 10-Year Retrospective Study

Pattern and Survival of Childhood Malignancies: A 10-Year Retrospective Study

Spectrum and Clinical Characteristics of Gene Mutations in Chinese Pediatric Acute Lymphoblastic Leukemia

PHF6 Mutations in Hematologic Malignancies

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