Myeloid/lymphoid neoplasms with FGFR1 rearrangement are a rare entity. We present a multicenter experience of 17 patients with FISH-confirmed FGFR1 rearrangement. The clinical presentation at diagnosis included myeloproliferative neoplasm (MPN) in 4 (24%) patients, acute leukemia (AL) in 7 (41%), and concomitant MPN with AL in 6 (35%). The two most frequently observed cytogenetic abnormalities were t(8;13)(p11.2;q12)(partner gene ZMYM2) and t(8;22)(p11.2; q11.2)(BCR). Seventy-eight percent of tested patients had a RUNX1 mutation, of whom all had AL. Overall response rate to frontline therapy was 69%, and 76% of patients subsequently received allogeneic stem cell transplant (ASCT). After a median follow-up of 11 months, median progression-free survival was 15 months and median overall survival was not reached. In conclusion, FGFR1-rearranged hematologic malignancies present with features of MPN and/or AL. FGFR1 and RUNX1 are therapeutic targets for ongoing and future clinical trials.
Drug reaction with eosinophilia and systemic symptom syndrome is a potentially fatal drug reaction that must be recognized quickly. Ipilimumab and nivolumab are both important agents in the treatment of melanoma and continue to be studied in other malignancies. We believe the mainstay of therapy for immunotherapy-induced drug reaction with eosinophilia and systemic symptom syndrome is early recognition, discontinuation of the inciting agent, supportive care, and treatment with high dose corticosteroids with appropriate tapers that may reduce the length of internal organ injury in cases with liver or kidney involvement.
Key Points
VTE developed in 11% of lymphoma patients after CAR T-cell therapy and was managed safely with anticoagulation. Coagulation abnormalities after CAR T-cell therapy occur but do not commonly lead to bleeding events.
Cancer biologists and other healthcare researchers face an increasing challenge in addressing the molecular complexity of disease. Biomarker measurement tools and techniques now contribute to both basic science and translational research. In particular, liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM) for multiplexed measurements of protein biomarkers has emerged as a versatile tool for systems biology. Assays can be developed for specific peptides that report on protein expression, mutation, or post-translational modification; discovery proteomics data rapidly translated into multiplexed quantitative approaches. Complementary advances in affinity purification enrich classes of enzymes or peptides representing post-translationally modified or chemically labeled substrates. Here, we illustrate the process for the relative quantification of hundreds of peptides in a single LC-MRM experiment. Desthiobiotinylated peptides produced by activity-based protein profiling (ABPP) using ATP probes and tyrosine-phosphorylated peptides are used as examples. These targeted quantification panels can be applied to further understand the biology of human disease.
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