Login Register Cart 0
Generic placeholder image

Current Pharmacogenomics and Personalized Medicine

Editor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Case Report

A Rare PTPN11 Mutation in a Patient with Juvenile Myelomonocytic Leukemia: A Case Report

Author(s): Shaghayegh Khanmohammadi, Samaneh Zoghi, Elham Rayzan, Sepideh Shahkarami, Raul Jimenez Heredia, Alexandra Frohne, Simin Seyedpour, Kaan Boztug and Nima Rezaei*

Volume 19, Issue 2, 2022

Published on: 15 December, 2022

Page: [112 - 117] Pages: 6

DOI: 10.2174/1875692120666221124113404

Price: $65

Abstract

Background: Juvenile myelomonocytic leukemia (JMML) is a rare childhood disease characterized by hepatosplenomegaly, monocytosis, anemia, increased white blood cell count, thrombocytopenia, skin infiltration, and elevated fetal hemoglobin. Mutation in specific genes, including KRAS, NRAS, PTPN11, and NF1, can lead to the development of JMML.

Case Presentation: A two-year-old boy with a history of inguinal abscess at the age of 12 months and surgery due to infectious lymphadenitis was referred to the hospital. His parents also reported a history of oral candidiasis, recurrent otitis media, and lymphadenopathy in the patient. The physical examination showed splenomegaly, macular rash, lymphadenopathy in the neck region, and rashes in the inguinal region and on the hands and feet. Laboratory and flow cytometry data showed lymphocytosis, low hemoglobin, thrombocytopenia, monocytosis, eosinophilia, and a shift to the left in the peripheral blood. The bone marrow aspiration showed a cellular marrow with myeloid hyperplasia. Whole-exome sequencing revealed a rare heterozygous ENST00000351677.2:c.1508G>C, p.Gly503Ala variant in PTPN11. The patient was diagnosed with JMML but, unfortunately, passed away.

Conclusion: We report a rare heterozygous mutation in the PTPN11 gene in a two-year-old boy diagnosed with JMML. This uncommon mutation should be considered in the mutational screening protocol of JMML. Management of JMML with RAS pathway targeted therapy may also have promising results and needs further investigations.

Keywords: Juvenile myelomonocytic leukemia, PTPN11, RAS pathway, rare disease, RAS-activating mutations, anemia.

« Previous Next »
Graphical Abstract

[1]
Caye A, Strullu M, Guidez F, et al. Juvenile myelomonocytic leukemia displays mutations in components of the RAS pathway and the PRC2 network. Nat Genet 2015; 47(11): 1334-40.
[http://dx.doi.org/10.1038/ng.3420] [PMID: 26457648]
[2]
Emi H. Juvenile myelomonocytic leukemia: UpToDate 2019. Available from: https://www.uptodate.com/contents/juvenile-myelomonocytic-leukemia?source=history_widget
[3]
de Vries ACH, Zwaan CM, Heuvel-Eibrink MM. Molecular basis of juvenile myelomonocytic leukemia. Haematologica 2010; 95(2): 179-82.
[http://dx.doi.org/10.3324/haematol.2009.016865] [PMID: 20139388]
[4]
Yoshimi A, Kojima S, Hirano N. Juvenile myelomonocytic leukemia: Epidemiology, etiopathogenesis, diagnosis, and management considerations. Paediatr Drugs 2010; 12(1): 11-21.
[http://dx.doi.org/10.2165/11316200-000000000-00000] [PMID: 20034338]
[5]
Flotho C, Steinemann D, Mullighan CG, et al. Genome-wide single-nucleotide polymorphism analysis in juvenile myelomonocytic leukemia identifies uniparental disomy surrounding the NF1 locus in cases associated with neurofibromatosis but not in cases with mutant RAS or PTPN11. Oncogene 2007; 26(39): 5816-21.
[http://dx.doi.org/10.1038/sj.onc.1210361] [PMID: 17353900]
[6]
Miao Y, Li B, Ding L, et al. PTPN11 mutation with additional somatic alteration indicates unfavorable outcome in juvenile myelomonocytic leukemia: A retrospective clinical study from a single center. Eur J Pediatr 2020; 179(3): 463-72.
[http://dx.doi.org/10.1007/s00431-019-03468-8] [PMID: 31807902]
[7]
Gupta AK, Meena JP, Chopra A, Tanwar P, Seth R. Juvenile myelomonocytic leukemia-A comprehensive review and recent advances in management. Am J Blood Res 2021; 11(1): 1-21.
[PMID: 33796386]
[8]
Liu X, Qu CK. Protein tyrosine phosphatase SHP-2] (PTPN11) in hematopoiesis and leukemogenesis. J Signal Transduct 2011; 2011: 1-8.
[http://dx.doi.org/10.1155/2011/195239] [PMID: 21799948]
[9]
Matozaki T, Murata Y, Saito Y, Okazawa H, Ohnishi H. Protein tyrosine phosphatase SHP-2: A proto-oncogene product that promotes Ras activation. Cancer Sci 2009; 100(10): 1786-93.
[http://dx.doi.org/10.1111/j.1349-7006.2009.01257.x] [PMID: 19622105]
[10]
Protein-tyrosine phosphatase, nonreceptor-type, 11; PTPN11 2020. Available from: https://www.omim.org/entry/176876
[11]
Sobreira NLM, Cirulli ET, Avramopoulos D, et al. Whole-genome sequencing of a single proband together with linkage analysis identifies a Mendelian disease gene. PLoS Genet 2010; 6(6): e1000991.
[http://dx.doi.org/10.1371/journal.pgen.1000991] [PMID: 20577567]
[12]
Ozen A, Comrie WA, Ardy RC, et al. CD55 deficiency, early-onset protein-losing enteropathy, and thrombosis. N Engl J Med 2017; 377(1): 52-61.
[http://dx.doi.org/10.1056/NEJMoa1615887] [PMID: 28657829]
[13]
Salzer E, Cagdas D, Hons M, et al. RASGRP1 deficiency causes immunodeficiency with impaired cytoskeletal dynamics. Nat Immunol 2016; 17(12): 1352-60.
[http://dx.doi.org/10.1038/ni.3575] [PMID: 27776107]
[14]
Bousfiha A, Jeddane L, Picard C, et al. Human inborn errors of immunity: 2019 update of the IUIS phenotypical classification. J Clin Immunol 2020; 40(1): 66-81.
[http://dx.doi.org/10.1007/s10875-020-00758-x] [PMID: 32048120]
[15]
Kager L, Jimenez Heredia R, Hirschmugl T, et al. Targeted mutation screening of 292 candidate genes in 38 children with inborn haematological cytopenias efficiently identifies novel disease-causing mutations. Br J Haematol 2018; 182(2): 251-8.
[http://dx.doi.org/10.1111/bjh.15389] [PMID: 29797310]
[16]
Tartaglia M, Niemeyer CM, Fragale A, et al. Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia. Nat Genet 2003; 34(2): 148-50.
[http://dx.doi.org/10.1038/ng1156] [PMID: 12717436]
[17]
Ortiz MV, Skoda-Smith S, Rauen KA, Allan RW, Slayton WB. Juvenile myelomonocytic leukemia in a 16-year-old with Noonan syndrome: Case report. J Pediatr Hematol Oncol 2012; 34(7): 569-72.
[http://dx.doi.org/10.1097/MPH.0b013e31824e192a] [PMID: 22510777]

Rights & Permissions Print Cite
Article Metrics
26
3
© 2024 Bentham Science Publishers | Privacy Policy