A Comparative Study of Molecular Characteristics of Diffuse Large B-cell Lymphoma from Patients with and without Human Immunodeficiency Virus Infection

Abstract

Purpose HIV-related diffuse large B-cell lymphoma (DLBCL) may be biologically different from DLBCL in the general population. We compared, by HIV status, the expression and prognostic significance of selected oncogenic markers in DLBCL diagnosed at Kaiser Permanente in California, between 1996 and 2007. Experimental Design Eighty HIV-infected DLBCL patients were 1:1 matched to 80 HIV-uninfected DLBCL patients by age, gender, and race. Twenty-three markers in the following categories were examined using IHC: (i) cell-cycle regulators, (ii) B-cell activators, (iii) antiapoptotic proteins, and (iv) others, such as IgM. Tumor marker expression was compared across HIV infection status by Fisher exact test. For markers differentially expressed in HIV-related DLBCL, logistic regression was used to evaluate the association between tumor marker expression and 2-year overall mortality, adjusting for International Prognostic Index, cell-of-origin phenotype, and DLBCL morphologic variants. Results Expression of cMYC (% positive in HIV-related and -unrelated DLBCL: 64% vs. 32%), BCL6 (45% vs. 10%), PKC-β2 (61% vs. 4%), MUM1 (59% vs. 14%), and CD44 (87% vs. 56%) was significantly elevated in HIV-related DLBCLs, whereas expression of p27 (39% vs. 75%) was significantly reduced. Of these, cMYC expression was independently associated with increased 2-year mortality in HIV-infected patients [relative risk = 3.09 (0.90–10.55)] in multivariable logistic regression. Conclusion These results suggest that HIV-related DLBCL pathogenesis more frequently involves cMYC and BCL6 among other factors. In particular, cMYC-mediated pathogenesis may partly explain the more aggressive clinical course of DLBCL in HIV-infected patients.

Frontline Science: c-Myc regulates P-selectin glycoprotein ligand-1 expression in monocytes during HIV-1 infection

“…Importantly, these results suggest that c-Myc/MAX dimerization is required for PSGL-1 induction. Whereas more will need to be done to confirm the role of c-Myc in PSGL-1 regulation, these data corroborate a recent report [60] and provide evidence that c-Myc is likely Figure 6. Boolean network model reveals signaling dynamics downstream of sCD40L + glutamate treatment of monocytes and predicts c-Myc as a likely regulator of PSGL-1 induction.…”

Population‐based outcome analysis of diffuse large B‐cell lymphoma in people living with HIV infection and competent individuals

“…Diffuse large B‐cell lymphomas (DLBCL) represent the commonest type of acquired immunodeficiency syndrome (AIDS)‐related lymphoma (ARL) and are clinically and biologically aggressive . The genetic events underlying the pathogenesis of AR‐DLBCL do not fully overlap with those observed in IC patients …”

“…Clinically, whilst the standard therapy for DLBCL in IC patients (IC‐DLBCL) is chemotherapy combined with rituximab, there are still open issues in the management of AR‐DLBCL, mainly regarding the optimal chemotherapy programs and the utility of rituximab . Moreover, there are conflicting data on the outcome of AR‐DLBCL patients when compared with IC‐DLBCL . The present study was designed to allow the comparison of a series of consecutive AR‐DLBCL patients from the Swiss HIV Cohort Study (SHCS) and a series of consecutive IC‐DLBCL patients from 2 centres in Switzerland and Northern Italy.…”

B cell lymphoma with IRF4 rearrangement: A clinicopathological study of 13 cases

“…Herein, we found that a patient with HIV‐associated large B cell lymphoma with IRF4 rearrangement of the salivary gland experienced favorable outcomes following treatment. This is noteworthy, as HIV‐associated large B cell lymphoma is generally aggressive and associated with a poor prognosis 19 . This suggests that IRF4 rearrangement may have altered disease course in this patient, emphasizing the importance of genetic testing in patients suffering from HIV‐associated lymphoproliferative disorders.…”