DOCK family genes encode evolutionarily conserved guanine nucleotide exchange factors for Rho GTPase involving multiple biological functions. Yet the patterns and prognostic significance of their expression in acute myeloid leukemia (AML) remain unexplored. Here we analyzed the expression patterns of 11 DOCK family genes in AML cells based on the array data of 347 patients from our cohort and several other published datasets. We further focused on the implications of the expression of DOCK1 since it was the only one in DOCK family to be associated with survival. Physiological functions and biological pathways associated with DOCK1 were identified using bioinformatics approaches. With a median follow up of 57 months, higher DOCK1 expression was associated with shorter disease free and overall survival. The finding could be validated by two independent cohorts. Multivariate analysis showed higher DOCK1 expression as a strong independent unfavorable prognostic factor. Higher DOCK1 expression was closely associated with older age, higher platelet and peripheral blast counts, intermediate-risk cytogenetics, FLT3-ITD, MLL-PTD and mutations in PTPN11, NPM1, RUNX1, ASXL1 and DNMT3A. Functional enrichment analysis suggested the association of DOCK1 overexpression with several key physiological pathways including cell proliferation, motility, and chemotaxis. Therefore, we suggested that AML with higher DOCK1 expression showed characteristic clinical and biological features. DOCK1 expression is an important prognostic marker and a potential therapeutic target for the treatment of AML. Studies in large prospective cohorts are necessary to confirm our findings. Further mechanistic studies to delineate the role of DOCK1 in the leukemogenesis are warranted.
Primary cardiac lymphoma (PCL) is very rare, with the variable clinical manifestations potentially leading to a delayed diagnosis. PCL is usually detected incidentally through image studies, whereas the diagnosis can be confirmed via analysis of pericardial effusion, endomyocardial biopsy tissue, or surgical specimens. Although no standard therapy has been established for PCL, without treatment, the prognosis is grave, with the estimated overall survival being approximately 1 year. We report a difficult diagnosis and complicated case of fulminant PCL, which is the first comprehensively reported case of PCL with secondary hemophagocytosis. A man presented with progressive dyspnea for 3 weeks, and then sudden cardiac death with ventricular fibrillation occurred. After resuscitation, echocardiography revealed a thickened left ventricular wall and severe mitral regurgitation, and computed tomography showed a right atrial mass with diffuse myocardial lesions. PCL was confirmed through a pathological analysis of specimens collected during mitral valvuloplasty, which also implied extensive myocardial involvement. Bone marrow biopsy demonstrated no evidence of lymphoma involvement, but secondary hemophagocytosis was noted. Despite aggressive chemotherapy, the patient died of sepsis with multiorgan failure 26 days after the operation.
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