PCM1-JAK2Fusion Tyrosine Kinase Gene-Related Neoplasia: A Systematic Review of the Clinical Literature

Abstract

Background This review summarizes the case studies of PCM1-JAK2 fusion tyrosine kinase gene-related neoplasia. Recommended treatment includes JAK2 inhibitors and hematologic stem cell transplantation (HSCT), although the small number of patients has limited study of their efficacy. Herein, we present all available cases in the current searchable literature with their demographics, diagnoses, treatments, and outcomes. Methods PubMed, ScienceDirect, Publons, the Cochrane Library, and Google were searched with the following terms: PCM1-JAK2, ruxolitinib and myeloid/lymphoid. Results Sixty-six patients (mean age = 50, 77% male) had an initial diagnosis of myeloproliferative neoplasm (MPN) in 40, acute leukemia in 21 and T-cell cutaneous lymphoma in 5. Thirty-five patients (53%) had completed 5-year follow-up. The 5-year survival for the MPN, acute myelogenous leukemia (AML), acute lymphocytic leukemia, and lymphoma groups are 62.7, 14.9%, 40.0%, and 100%, respectively. Too few patients have been treated with ruxolitinib to draw conclusions regarding its effect on survival while the 5-year survival for MPN patients with or without HSCT was 80.2% (40.3%-94.8%) versus 51.5% (22.3%-74.6%), respectively. The T-cell cutaneous lymphoma patients have all survived at least 7 years. Conclusion This rare condition may be increasingly detected with wider use of genomics. Ruxolitinib can yield hematologic and molecular remissions. However, HSCT is, at this time, the only potentially curative treatment. Useful prognostic markers are needed to determine appropriate timing for HSCT in patients with MPN. Patients presenting with acute leukemia have a poor prognosis.

NUP214 fusion genes in acute leukemias: genetic characterization of rare cases

“…( 35 ) in a patient suffering from a rare, aggressive myeloid neoplasia with eosinophilia; treatment with futibatinib , an oral selective small molecule inhibitor of FGFR1-4, resulted in complete hematologic and cytogenetic remission ( 35 ). The PCM1 gene as partner in the chimera PCM1::JAK2 has been implicated in the pathogenesis of also other acute myeloid/lymphoid neoplasms ( 36 ) whereas rearrangements of FGFR1 are rare ( 37 ). The use of selective TKIs can potentially affect outcomes in these patients ( 35 , 37 ).…”

The international consensus classification of eosinophilic disorders and systemic mastocytosis

“…For cases with PCM1::JAK2 fusion, the disease course can be highly variable. 22,74 In patients presenting in chronic phase of a myeloid neoplasm, the disease may be indolent with a 5-year survival up to 80%. 14,22,74 On the other hand, in patients who present or progress to acute leukemia, the prognosis is dismal.…”

“…22,74 In patients presenting in chronic phase of a myeloid neoplasm, the disease may be indolent with a 5-year survival up to 80%. 14,22,74 On the other hand, in patients who present or progress to acute leukemia, the prognosis is dismal. Targeted therapy with JAK2 inhibitors such as ruxolitinib may offer some but limited benefit 24,75 and should be used to bridge patients to allogeneic SCT, which can lead to durable disease-free survival.…”

Myeloid/lymphoid neoplasms associated with eosinophilia and rearrangements of <i>PCM1::JAK2</i> with erythroblastic sarcoma: a case report and literature review

“…The reason for the male preponderance is not clear. 8 Lierman et al, number of patients reported precludes a definitive statement regarding its effect on survival. Further studies are needed to determine how best to utilize ruxolitinib.…”

“…Therefore, currently, ASCT is still the only way to cure the disease, particularly in the absence of acute leukemia. 8 For those patients who are unsuitable for transplantation, the prospect seems very bleak. Some patients with MPN received hydroxyurea or interferon for initial treatment and then followed a strategy of watch and wait.…”