The Combination of Allele Burden and Expression Can Be Helpful in Distinguishing the Subtype of MPN Patients

Overview

Journal Cancer Control

Specialty Oncology

Date 2023 Mar 10

PMID 36895113

Authors

Sanyun Wu

Ping Luo

Tuerxunayi Rouzi

Yalan Yu

Bei Xiong

Yingying Wang

Xuelan Zuo

Affiliations

Soon will be listed here.

Abstract

Introduction: Classical Philadelphia-negative myeloproliferative neoplasm (MPN) includes Essential Thrombocythemia (ET), Polycythemia Vera (PV) and Primary Myelofibrosis (PMF). The mutation is part of the major criteria for diagnosis of MPN. is reported to be highly overexpressed in most hematological malignancy. Our aim was to explore the combination value of allele burden and expression in distinguishing the subtype of MPN patients.

Methods: Allele specific real-time quantitative fluorescence PCR (AS-qPCR) was conducted to detect allele burden. expression was assessed by RQ-PCR. Our study is a retrospective study.

Results: allele burden and expression were different in MPN subgroups. The expression of in PMF and PV is higher than in ET. allele burden in PMF and PV is also higher than in ET. ROC analysis indicated that combination of allele burden and expression to discriminate ET and PV, ET and PMF, PV and PMF is 0.956, 0.871, 0.737 respectively. Furthermore, their ability to distinguish ET patients with high Hb levels from PV patients with high platelet counts is 0.891.

Conclusions: Our data revealed that combination of allele burden and expression is useful in distinguishing the subtype of MPN patients.

Citing Articles

Detection and quantification of JAK2V617F copy number by droplet digital PCR versus real-time PCR.

Wu S, Li Y, Huang R, Li T, Yu Y, Luo P Ann Hematol. 2023; 103(2):421-426.

PMID: 37968422 DOI: 10.1007/s00277-023-05544-4.

References

Barbui T, Thiele J, Gisslinger H, Kvasnicka H, Vannucchi A, Guglielmelli P . The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion. Blood Cancer J. 2018; 8(2):15. PMC: 5807384. DOI: 10.1038/s41408-018-0054-y. View

Barbui T, Thiele J, Carobbio A, Guglielmelli P, Rambaldi A, Vannucchi A . Discriminating between essential thrombocythemia and masked polycythemia vera in JAK2 mutated patients. Am J Hematol. 2014; 89(6):588-90. DOI: 10.1002/ajh.23694. View

Kvasnicka H, Thiele J . Prodromal myeloproliferative neoplasms: the 2008 WHO classification. Am J Hematol. 2009; 85(1):62-9. DOI: 10.1002/ajh.21543. View

Barbui T, Thiele J, Passamonti F, Rumi E, Boveri E, Ruggeri M . Survival and disease progression in essential thrombocythemia are significantly influenced by accurate morphologic diagnosis: an international study. J Clin Oncol. 2011; 29(23):3179-84. DOI: 10.1200/JCO.2010.34.5298. View

Guglielmelli P, Pacilli A, Rotunno G, Rumi E, Rosti V, Delaini F . Presentation and outcome of patients with 2016 WHO diagnosis of prefibrotic and overt primary myelofibrosis. Blood. 2017; 129(24):3227-3236. DOI: 10.1182/blood-2017-01-761999. View

Stuckey R, Gomez-Casares M . Recent Advances in the Use of Molecular Analyses to Inform the Diagnosis and Prognosis of Patients with Polycythaemia Vera. Int J Mol Sci. 2021; 22(9). PMC: 8126083. DOI: 10.3390/ijms22095042. View

Barbui T, Thiele J, Carobbio A, Gisslinger H, Finazzi G, Rumi E . Masked polycythemia vera diagnosed according to WHO and BCSH classification. Am J Hematol. 2013; 89(2):199-202. DOI: 10.1002/ajh.23617. View

Tang G, Sydney Sir Philip J, Weinberg O, Tam W, Sadigh S, Lake J . Hematopoietic neoplasms with 9p24/JAK2 rearrangement: a multicenter study. Mod Pathol. 2018; 32(4):490-498. DOI: 10.1038/s41379-018-0165-9. View

Guglielmelli P, Zini R, Bogani C, Salati S, Pancrazzi A, Bianchi E . Molecular profiling of CD34+ cells in idiopathic myelofibrosis identifies a set of disease-associated genes and reveals the clinical significance of Wilms' tumor gene 1 (WT1). Stem Cells. 2006; 25(1):165-73. DOI: 10.1634/stemcells.2006-0351. View

10.

Langabeer S, Andrikovics H, Asp J, Bellosillo B, Carillo S, Haslam K . Molecular diagnostics of myeloproliferative neoplasms. Eur J Haematol. 2015; 95(4):270-9. DOI: 10.1111/ejh.12578. View

11.

Tefferi A . Primary myelofibrosis: 2021 update on diagnosis, risk-stratification and management. Am J Hematol. 2020; 96(1):145-162. DOI: 10.1002/ajh.26050. View

12.

Montano G, Vidovic K, Palladino C, Cesaro E, Sodaro G, Quintarelli C . WT1-mediated repression of the proapoptotic transcription factor ZNF224 is triggered by the BCR-ABL oncogene. Oncotarget. 2015; 6(29):28223-37. PMC: 4695056. DOI: 10.18632/oncotarget.4950. View

13.

Kralovics R, Passamonti F, Buser A, Teo S, Tiedt R, Passweg J . A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005; 352(17):1779-90. DOI: 10.1056/NEJMoa051113. View

14.

Cook A, Li L, Ho Y, Lin A, Li L, Stein A . Role of altered growth factor receptor-mediated JAK2 signaling in growth and maintenance of human acute myeloid leukemia stem cells. Blood. 2014; 123(18):2826-37. PMC: 4007609. DOI: 10.1182/blood-2013-05-505735. View

15.

Thomas S, Krishnan A . Platelet Heterogeneity in Myeloproliferative Neoplasms. Arterioscler Thromb Vasc Biol. 2021; 41(11):2661-2670. PMC: 8551046. DOI: 10.1161/ATVBAHA.121.316373. View

16.

Rautenberg C, Germing U, Pechtel S, Lamers M, Fischermanns C, Jager P . Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS. Blood Cancer J. 2019; 9(11):86. PMC: 6851368. DOI: 10.1038/s41408-019-0248-y. View

17.

Zhang Y, Yan W, Yang Z, Li Y, Tan X, Jiang J . The role of WT1 in breast cancer: clinical implications, biological effects and molecular mechanism. Int J Biol Sci. 2020; 16(8):1474-1480. PMC: 7085227. DOI: 10.7150/ijbs.39958. View

18.

Azevedo A, Silva S, Reichert A, Lima F, Junior E, Rueff J . Prevalence of the Janus kinase 2 V617F mutation in Philadelphia-negative myeloproliferative neoplasms in a Portuguese population. Biomed Rep. 2017; 7(4):370-376. PMC: 5649586. DOI: 10.3892/br.2017.977. View

19.

Gallo D, Nicoli P, Calabrese C, Gaidano V, Petiti J, Rosso V . The Wilms' tumor (WT1) gene expression correlates with the International Prognostic Scoring System (IPSS) score in patients with myelofibrosis and it is a marker of response to therapy. Cancer Med. 2016; 5(7):1650-3. PMC: 4867666. DOI: 10.1002/cam4.735. View

20.

Carobbio A, Finazzi G, Antonioli E, Guglielmelli P, Vannucchi A, Dellacasa C . JAK2V617F allele burden and thrombosis: a direct comparison in essential thrombocythemia and polycythemia vera. Exp Hematol. 2009; 37(9):1016-21. PMC: 2746993. DOI: 10.1016/j.exphem.2009.06.006. View