[Clinical Features and Prognosis of Childhood B-lineage Acute Lymphoblastic Leukemia Expressing the Gene]

Overview

Journal Zhongguo Dang Dai Er Ke Za Zhi

Specialty Pediatrics

Date 2022 Jun 1

PMID 35644195

Authors

Feng Zhang

Ai-Dong Lu

Ying-Xi Zuo

Ming-Ming Ding

Yue-Ping Jia

Le-Ping Zhang

Affiliations

Soon will be listed here.

Abstract

Objectives: To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma () gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL).

Methods: A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the gene and 97 were negative. None of the children were positive for -, /, , or . The positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors.

Results: Compared with the negative group, the positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (<0.05). There was a significant reduction in the copy number after induction chemotherapy (<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the copy number was not correlated with the MRD level (>0.05). In the MRD negative group, there was also no correlation between them (>0.05). The positive group had a significantly higher 4-year event-free survival rate than the negative group (87.5%±4.6% vs 73.5%±4.6%, <0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, >0.05). The Cox proportional-hazards regression model analysis showed that positive expression was a protective factor for event-free survival rate in children with B-ALL (<0.05).

Conclusions: Although the gene cannot be monitored as MRD, overexpression of suggests a good prognosis in B-ALL.

References

Inaba H, Mullighan C . Pediatric acute lymphoblastic leukemia. Haematologica. 2020; 105(11):2524-2539. PMC: 7604619. DOI: 10.3324/haematol.2020.247031. View

Qin Y, Zhu H, Jiang B, Li J, Lu X, Li L . Expression patterns of WT1 and PRAME in acute myeloid leukemia patients and their usefulness for monitoring minimal residual disease. Leuk Res. 2008; 33(3):384-90. DOI: 10.1016/j.leukres.2008.08.026. View

Zhang Y, Lu A, Yang L, Li L, Chen W, Long L . PRAME overexpression predicted good outcome in pediatric B-cell acute lymphoblastic leukemia patients receiving chemotherapy. Leuk Res. 2016; 52:43-49. DOI: 10.1016/j.leukres.2016.11.005. View

Huang Z, Jia Y, Ruan G, Zuo Y, Wu J, Lu A . Quantitative analysis of IKZF1 gene deletions in pediatric B-cell precursor acute lymphoblastic leukemia: higher levels are associated with a poorer prognosis. Pediatr Hematol Oncol. 2021; 39(3):243-253. DOI: 10.1080/08880018.2021.1966558. View

Matsushita M, Ikeda H, Kizaki M, Okamoto S, Ogasawara M, Ikeda Y . Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol. 2001; 112(4):916-26. DOI: 10.1046/j.1365-2141.2001.02670.x. View

Tanaka N, Wang Y, Shiseki M, Takanashi M, Motoji T . Inhibition of PRAME expression causes cell cycle arrest and apoptosis in leukemic cells. Leuk Res. 2011; 35(9):1219-25. DOI: 10.1016/j.leukres.2011.04.005. View

El Khateeb E, Morgan D . Preferentially Expressed Antigen of Melanoma (PRAME) and Wilms' Tumor 1 (WT 1) Genes Expression in Childhood Acute Lymphoblastic Leukemia, Prognostic Role and Correlation with Survival. Open Access Maced J Med Sci. 2016; 3(1):57-62. PMC: 4877789. DOI: 10.3889/oamjms.2015.001. View

Schwab C, Harrison C . Advances in B-cell Precursor Acute Lymphoblastic Leukemia Genomics. Hemasphere. 2019; 2(4):e53. PMC: 6746003. DOI: 10.1097/HS9.0000000000000053. View

Carroll A, Shago M, Mikhail F, Raimondi S, Hirsch B, Loh M . Masked hypodiploidy: Hypodiploid acute lymphoblastic leukemia (ALL) mimicking hyperdiploid ALL in children: A report from the Children's Oncology Group. Cancer Genet. 2019; 238:62-68. PMC: 6768693. DOI: 10.1016/j.cancergen.2019.07.009. View

10.

Arber D, Orazi A, Hasserjian R, Thiele J, Borowitz M, Le Beau M . The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016; 127(20):2391-405. DOI: 10.1182/blood-2016-03-643544. View

11.

Wang Y, Zeng H, Zhang L . ETV6/RUNX1-positive childhood acute lymphoblastic leukemia in China: excellent prognosis with improved BFM protocol. Ital J Pediatr. 2018; 44(1):94. PMC: 6097322. DOI: 10.1186/s13052-018-0541-6. View

12.

Abdelmalak C, Yahya R, Elghannam D, El-Khadragy A, Abd El Messih H . PRAME gene expression in childhood acute lymphoblastic leukemia: impact on prognosis. Clin Lab. 2014; 60(1):55-61. DOI: 10.7754/clin.lab.2013.121137. View

13.

Steinbach D, Hermann J, Viehmann S, Zintl F, Gruhn B . Clinical implications of PRAME gene expression in childhood acute myeloid leukemia. Cancer Genet Cytogenet. 2002; 133(2):118-23. DOI: 10.1016/s0165-4608(01)00570-2. View

14.

Spanaki A, Perdikogianni C, Linardakis E, Kalmanti M . Quantitative assessment of PRAME expression in diagnosis of childhood acute leukemia. Leuk Res. 2006; 31(5):639-42. DOI: 10.1016/j.leukres.2006.06.006. View

15.

Iacobucci I, Mullighan C . Genetic Basis of Acute Lymphoblastic Leukemia. J Clin Oncol. 2017; 35(9):975-983. PMC: 5455679. DOI: 10.1200/JCO.2016.70.7836. View

16.

Ding K, Wang X, Fu R, Ruan E, Liu H, Shao Z . PRAME Gene Expression in Acute Leukemia and Its Clinical Significance. Cancer Biol Med. 2013; 9(1):73-6. PMC: 3643640. DOI: 10.3969/j.issn.2095-3941.2012.01.013. View

17.

Ikeda H, Lethe B, Lehmann F, Van Baren N, Baurain J, De Smet C . Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity. 1997; 6(2):199-208. DOI: 10.1016/s1074-7613(00)80426-4. View

18.

Paydas S, Tanriverdi K, Yavuz S, Disel U, Baslamisli F, Burgut R . PRAME mRNA levels in cases with acute leukemia: clinical importance and future prospects. Am J Hematol. 2005; 79(4):257-61. DOI: 10.1002/ajh.20425. View

19.

Xue Y, Cheng Y, Lu A, Wang Y, Zuo Y, Yan C . Allogeneic Hematopoietic Stem Cell Transplantation, Especially Haploidentical, May Improve Long-Term Survival for High-Risk Pediatric Patients with Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia in the Tyrosine Kinase Inhibitor Era. Biol Blood Marrow Transplant. 2018; 25(8):1611-1620. DOI: 10.1016/j.bbmt.2018.12.007. View