Conventional Cytogenetic Analysis and Array CGH + SNP Identify Essential Thrombocythemia and Prefibrotic Primary Myelofibrosis Patients Who Are at Risk for Disease Progression

Joseph Tripodi; Ronald Hoffman; Douglas Tremblay; Daiva Ahire; John Mascarenhas; Marina Kremyanskaya; Vesna Najfeld

doi:10.3390/ijms25074061

Conventional Cytogenetic Analysis and Array CGH + SNP Identify Essential Thrombocythemia and Prefibrotic Primary Myelofibrosis Patients Who Are at Risk for Disease Progression

Int J Mol Sci. 2024 Apr 5;25(7):4061. doi: 10.3390/ijms25074061.

Authors

Joseph Tripodi¹, Ronald Hoffman², Douglas Tremblay², Daiva Ahire¹, John Mascarenhas², Marina Kremyanskaya², Vesna Najfeld^{1

2}

Affiliations

¹ Tumor CytoGenomics Laboratory, Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
² Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

Abstract

The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions.

Keywords: Comparative Genomic Hybridization + Single Nucleotide Polymorphism array; MPN disease progression; Philadelphia chromosome-negative myeloproliferative neoplasms; conventional cytogenetics; essential thrombocythemia; prefibrotic primary myelofibrosis.

MeSH terms

Comparative Genomic Hybridization
Cytogenetic Analysis
Disease Progression
Humans
Polymorphism, Single Nucleotide
Primary Myelofibrosis* / diagnosis
Primary Myelofibrosis* / genetics
Retrospective Studies
Thrombocythemia, Essential* / diagnosis
Thrombocythemia, Essential* / genetics

Grants and funding

This work was supported in part through the computational and data resources and staff expertise provided by Scientific Computing and Data at the Icahn School of Medicine at Mount Sinai and supported by the Clinical and Translational Science Awards (CTSA) grant UL1TR004419 from the National Center for Advancing Translational Sciences.