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Gene Expression Profiles May Provide Complementary Prognostic Information for MF

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The researchers of the study say their findings may aid the hematological community in determining the value of integrating gene expression profiles in contemporary prognostic models to better identify high-risk patients with a poor prognosis.

A proof-of-concept study suggests gene expression profiles (GEPs) of granulocytes may offer complementary prognostic information to current models of risk stratification for myelofibrosis (MF).

The researchers of the study say their findings may aid the hematological community in determining the value of integrating GEPs in contemporary prognostic models to better identify high-risk patients with poor prognoses.

They also note that future studies may prospectively validate their findings in an independent group of MF cases, which can help improve identification of patients with poorer prognoses who can benefit from clinical trials or allogeneic stem cell transplantation.

The GEPs of 144 patients were analyzed in the study, from which 201 survival-related transcripts emerged via a Cox-regression analysis. According to the researchers, they focused on granulocytes because they are an “easily accessible myeloid cell population that belongs to the neoplastic clone, unlike peripheral blood mononuclear cells that also contain lymphoid elements.”

The transcripts characterized patients who were at high risk of death, with these patients demonstrating both inferior overall survival (hazard ratio [HR] 4.736; 95% CI) and leukemia-free survival (HR 3.976; 95% CI) compared with patients characterized as low risk. Unsurprisingly, more pre-primary MF samples were characterized as low risk and more secondary MF samples were characterized as high risk.

High-risk patients also displayed clinical and molecular features typically associated with poor prognosis, like having high molecular risk mutations.

“Our results demonstrated that gene expression–based classification showed good agreement with contemporary prognostic models; indeed, the high-risk classification correlated with the presence of several detrimental features, such as advanced age, decreased hemoglobin (Hb) levels (<10 g/dL) and platelet count (<100 x 109/L), increased white blood cell count (>25 x 109/L), circulating blasts ≥1% and 2%, and the presence of constitutional symptoms and splenomegaly,” explained the researchers.

A large portion of high-risk patients harbored JAK2V617F mutations and there was an increased presence of homozygous mutations in this group. Meanwhile, low-risk patients more frequently harbored JAK2 heterozygosity.

Reference: Rontauroli S, Castellano S, Guglielmelli P, et al. Gene expression profile correlates with molecular and clinical features in patients with myelofibrosis. Blood Adv. 2021;5(5):1452-1462. doi:10.1182/bloodadvances.2020003614

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