The prognostic impact of non-driver gene mutations and variant allele frequency in primary myelofibrosis.

[PhysAssist]

The prognostic impact of non-driver gene mutations and variant allele frequency in primary myelofibrosis.

To the Editor:

Myelofibrosis is a Philadelphia-negative chronic myelo-proliferative-neoplasm (MPN) characterized by alteration of the JAK–STAT path-way, primarily through activating mutations in MPN driver genes(JAK2, CALR, and MPL).

However, patients usually have mutations in other genes related to myeloid neoplasms that may influence the clinical phenotype or treatment response (non-MPN driver genes).

Allogeneic hematopoietic stem cell transplantation (allo-HSCT)remains the only curative treatment, but given the significant mortality associated with the procedure, it is essential to identify high-risk patients who can benefit from it

The Mutation-Enhanced International Prognostic Score System(MIPSS70) and its subsequent update (MIPSS70+v2.0) integrate clinical, molecular (mutations inASXL1,SRSF2,EZH2, IDH1/2, andU2AF1genes), and cytogenetic data to identify high-risk patients in whom allo-HSCT should be considered.1,2Recently, the adverse prognostic significance ofASXL1mutations has been questioned, with their impact seemingly limited to primary myelofibrosis (PMF).3,4Moreover,several additional gene mutations not originally included in the MIPSS models have been associated with poor prognosis in PMF3. A recent study examined the prognostic value of mutations in NRAS, KRAS, CBL, RUNX1, and TP53genes in PMF, along with their contribution on the discriminative accuracy of the MIPSS models.5Considering the low frequency of these high-risk mutations, external validation of their findings is necessary. In the present study, approved by the institutional committee of the Spanish MPN Group (GEMFIN), our aim was to analyze the impact of non-MPN driver somatic mutations in PMF patients from 60 Spanish institutions. Out of a total of 581 patients with myelofibrosis (either PMF or secondary myelofibrosis after polycythemia vera or essential thrombocythemia) according to WHO criteria in use at the time of diagnosis, and with availability of molecular analysis by massive next-generation sequencing (NGS), we selected 312 patients with PMF for this analysis.

Remainder of study details available at source:

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