Impact of KRAS and NRAS mutations on outcomes in acute myeloid leukemia.

The prognostic significance of RAS mutations in AML is poorly understood. In this ambispective cohort study of 239 newly-diagnosed AML patients at the University of Maryland, we assessed the median overall survival (mOS) and median event-free survival (mEFS) in RAS wild-type (WT) AML (n = 196), KRAS-mutated AML (n = 11), NRAS-mutated AML (n = 25), and KRAS/NRAS-mutated AML (n = 7). We used propensity score to adjust outcomes. NRAS-mutated AML had a similar response rate to first-line treatment and mOS compared to RAS-WT AML (57 vs. 54%, p = 0.8, 22.7 vs. 14.6 months, p = 0.7). The mOS of KRAS-mutated AML was shorter compared to RAS-WT AML (p = 0.049) and NRAS-mutated AML (p = 0.02). KRAS-mutated AML treated with anthracycline-based first-line regimens had a lower relative mortality compared to treatment with hypomethylating agents with venetoclax (HR <0.01, p = 0.04) and without venetoclax (HR <0.01, p = 0.04). This study demonstrates that KRAS but not NRAS mutations are associated with worse outcomes in AML.NOVELTY STATEMENTWhat is the new aspect of your work? The clinical significance of RAS mutations remains poorly defined and prior studies have yielded conflicting results. We used causal inferential methods, propensity score modeling, to determine the impact of KRAS and NRAS mutation on survival in newly diagnosed AML patients, independent of other risk factors. Moreover, we analyzed the outcomes of KRAS and NRAS-mutated AML patients receiving first-line therapy with hypomethylating agents and other non-anthracycline-based regimens. We provided a detailed description of RAS-mutated AML, including co-occurring mutations and cytogenetic abnormalities.What is the central finding of your work? KRAS mutations but not NRAS mutations in AML are directly linked to worse outcomes even after controlling for differences in AML type, co-occurring cytogenetic changes, treatment regimens, and comorbidities. KRAS-mutated AML has a higher relative mortality when treated with a hypomethylating agent-based first-line induction regimen compared to treatment with an anthracycline-based regimen.What is (or could be) the specific clinical relevance of your work? Our findings can help refine our genetic profiles of AML, improve prognostic models, and better stratify treatment regimens.

A Case of Acute Myeloid Leukemia-Associated Necrotizing Sweet Syndrome.

Sweet syndrome (SS), or acute febrile neutrophilic dermatosis, is a rare painful skin condition that is characterized by hyperpyrexia, peripheral blood and skin neutrophilia, and edematous skin lesions. Necrotizing SS (NSS) is a severe and locally aggressive condition that histopathologically resembles a necrotizing soft tissue infection. As opposed to necrotizing soft tissue infections, NSS responds to systemic steroids. SS is divided into three subtypes: classical SS, malignancy-associated SS, and drug-induced SS. Within the malignancy-associated SS subtype, both solid tumor and hematologic malignancies have been precursors to developing SS. Here, we present a case of acute myeloid leukemia-associated NSS.

NTRK3 mutation in secretory carcinoma of the parotid gland: A Case report.

Mammary analog secretory carcinoma (MASC) is a newly described carcinoma with a molecular hallmark of ETV6-NTRK3 fusion that promotes oncogenesis. While MASC histopathology was well-studied in the literature, clinical behavior remains unstudied. We present a 22-year-old man with painless parotid mass, which was diagnosed as salivary gland cancer, MASC subtype.