Mohammed Abdulgayoom, Abdulrahman F Al-Mashdali, Awni Alshurafa, Mohammad S Afana, Anas M Babiker, Mohammad Bakheet, Shehab F Mohamed, Mohamed A Yassin
Reported cases with isolated del(5q) and an MPN driver mutation suggest a rare overlap presentation with mixed dysplastic and proliferative features. Lenalidomide appears to provide hematologic and cytogenetic benefit in some patients, although molecular persistence and progression to AML have been observed. Given the limited number and heterogeneity of published cases, these observations should be interpreted with caution. Larger, systematically collected datasets are needed to better understand the clinical significance and optimal management of this combination.
BACKGROUND: Myeloid neoplasms harboring both an isolated deletion of chromosome 5q (del(5q)) and myeloproliferative neoplasm (MPN) driver mutations (JAK2, CALR, MPL) constitute a rare and diagnostically challenging subset, often described with features overlapping those of myelodysplastic syndromes (MDS) and MPN.
METHODS: We systematically reviewed published case reports and case series of adult patients with myeloid neoplasms and concomitant isolated del(5q) and MPN driver mutations. A comprehensive search of PubMed and Google Scholar from inception through 31 December 2024 was performed using terms related to "del(5q)", "JAK2", "CALR", "MPL", and "myeloid neoplasm". Eligible reports required documentation of isolated del(5q) and at least one MPN driver mutation with extractable clinical, cytogenetic, and/or molecular data. Data were synthesised descriptively; no quantitative meta-analysis was feasible. The review followed PRISMA 2020 guidelines and was registered post-study at INPLASY2025120046.
RESULTS: Twenty publications reporting 24 patients (diagnosed between 2006 and 2021) met the inclusion criteria. The median age was 70.5 years with a female predominance. Most patients presented with macrocytic anemia, thrombocytosis, and megakaryocytic dysplasia, frequently accompanied by marrow fibrosis. JAK2 V617F was the predominant mutation, whereas CALR and MPL were rarely described. Lenalidomide achieved hematologic responses in 14 of 17 evaluable patients and cytogenetic responses in 8 of 16; JAK2 V617F clearance occurred in 4 of 13. During a median follow-up of approximately two years, 5 of 24 patients progressed to acute myeloid leukemia.
CONCLUSION: Reported cases with isolated del(5q) and an MPN driver mutation suggest a rare overlap presentation with mixed dysplastic and proliferative features. Lenalidomide appears to provide hematologic and cytogenetic benefit in some patients, although molecular persistence and progression to AML have been observed. Given the limited number and heterogeneity of published cases, these observations should be interpreted with caution. Larger, systematically collected datasets are needed to better understand the clinical significance and optimal management of this combination.