Page 55 - Haematologica Vol. 109 - July 2024

REVIEW ARTICLE - CXCL8 in primary myelofibrosis
G. Vermeersch et al.
ongoing.102,103 In November 2022, a phase I/II clinical trial of BMS-986253 monotherapy or in combination with DNA methyltransferase inhibitors within patients with MDS was initiated (clinicaltrials.gov 05148234). The estimated study completion date is in July 2025.104 We refer to the review of Tremblay et al. for an extensive description of other therapeutic targets beyond the CXCL8-CXCR1/2 axis such as TGF-b1 (AVID200) or PI3K (parsaclisib) in PMF.105 Whether CXCL8-CXCR1/2 inhibition is superior compared to these therapeutic targets is unknown.
Conclusion
With a median survival of 16-35 months for high-risk pa- tients, PMF shows the most aggressive characteristics amongst all MPN. Current therapeutic approaches such as JAK-inhibitors are ineffective in reducing progression of PMF or avoiding transformation into secondary AML. Aberrant megakaryopoiesis is a pathological hallmark within MPN, and megakaryocytes in myelofibrosis show higher proliferative capacities and morphologic abnor- malities such as hypolobulated nuclei and clustering. As multiple cytokines are increased in PB and BM of patients with PMF, various pathways may concomitantly contribute to its pathogenesis. The chemokine CXCL8 is of particu- lar interest within PMF, and MPN in general, as patients show increased concentrations within BM and PB inde- pendently of mutational status. Moreover, an increased concentration is associated with reduced OS and higher rates of secondary AML. The CXCL8-CXCR1/2 axis might play a central role within PMF pathogenesis as blockage
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Disclosures
No conflicts of interest to disclose.
Contributions
The authors met the criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). GV, SS and MG contributed to writing the manu- script. PP, SS, MG and TD critically revised the manuscript.
Acknowledgments
Figures created with BioRender.com.
Funding
No funding was received for this review.
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