The disturbance of apoptosis molecular signaling pathways is involved in carcinogenesis. BCL2 family of proteins is the hallmark of apoptosis regulation. In the last decade, new members ofBCL2gene family were discovered and cloned and were found to be differentially expressed in many types of cancer. BCL2 protein family, through its role in regulation of apoptotic pathways, is possibly related to cancer pathophysiology and resistance to conventional chemotherapy. It is well known that leukemias are haematopoietic malignancies characterized by biological diversity, varied cytogenetics, different immunophenotype profiles, and diverse outcome. Current research focuses on the prognostic impact and specific role of these proteins in the pathogenesis of leukemias. The understanding of the molecular pathways that participate in the biology of leukemias may lead to the design of new therapies which may improve patients' survival. In the present paper, we describe current knowledge on the role of BCL2 apoptosis regulator proteins in acute and chronic leukemias.

Gastrointestinal lymphoma is the most common form of extranodal lymphoma, accounting for 30%–40% of cases. The most commonly involved site is the stomach (60%–75% of cases), followed by the small bowel, ileum, cecum, colon and rectum. The most common histological subtypes are diffuse large B-cell lymphoma (DLBCL) and marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT). Helicobacter pylori infection has been implicated in the pathogenesis of MALT gastric lymphoma, but its role in gastric diffuse large B-cell non-Hodgkin's lymphoma (NHL) is controversial. The therapeutic approach for patients with gastric NHL has been revised over the last 10 years. Conservative treatment with anthracycline-based chemotherapy alone or in combination with involved-field radiotherapy has replaced gastrectomy as standard therapy in cases with DLBCL. Additionally, MALT lymphomas are mainly treated with antibiotics alone, which can induce lasting remissions in those cases associated with H. pylori infection. Nevertheless, various therapeutic aspects for primary gastric lymphomas are still controversial and several questions remain unanswered. Among others, the role of rituximab, consolidation radiotherapy as well as H. pylori eradication in histological aggressive subtypes warrants better clarification.

The aim of this retrospective study was to illustrate the clinicopathologic data and the treatment results in patients with primary gastrointestinal tract non-Hodgkin's lymphoma (GI NHL). Among 810 patients with NHL, 128 cases (15.8%) were diagnosed as primary GI tract NHL. There were 79 males and 49 females with median age of 62 years. The most common primary site was the stomach (68%). Overall, 67.2% of the patients were in stages I – II, and 32.8% in stages III – IV. Simultaneous involvement of the GI tract and other extranodal sites was observed in 26 patients (20%). Extranodal marginal zone B-cell lymphoma (MZBL) (i.e., low-grade lymphoma of mucosa-associated lymphoid tissue type) accounted for 48.4% of lymphomas. Aggressive lymphomas (diffuse large B-cell lymphoma [DLBL]) accounted for 44.5%. Eighty-three patients (67.5%) achieved complete response (CR), either by surgery (43/43 patients, 17 with DLBL and 25 with MZBL) or by primary chemotherapy (40/64 patients, 22 with DLBL and 17 with MZBL). Sixty-two patients remain in CR; 33/43 after surgical resection (13/17 with DLBL and 20/25 patients with MZBL), and 29/40 after only chemotherapy (18/22 with DLBL and 10/17 with MZBL). The major prognostic factor for outcome in the present study was the stage of the disease. Patients with localized lymphoma (stage I and II) had significantly longer DFS and OS (DFS and OS at 3-year: 83% and 87%, respectively) than patients with extended disease (stage III and IV) (DFS and OS at 3-year: 46% and 60%, respectively) (P < 0.0001). The International Prognostic Index (IPI) for patients with aggressive lymphomas was prognostic only for DFS (79% for low-risk patients [IPI score 0 – 1] vs 49% for higher risk groups [IPI score >1] at 3-year, P = 0.0131).

Learning Objectives: After completing this course, the reader will be able to: Describe the effect of the addition of rituximab to standard CHOP chemotherapy on the outcome of patients with primary mediastinal large B-cell lymphoma.Explain potential changes in the use of radiotherapy and aggressive chemotherapy in the rituximab era.This article is available for continuing medical education credit at CME.TheOncologist.comMore aggressive treatment approaches (methotrexate, cytarabine, cyclophosphamide, vincristine, prednisone, and bleomycin [the MACOP-B regimen] or consolidation with high-dose therapy and autologous stem cell transplantation) have been considered to be superior to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with primary mediastinal large B-cell lymphoma (PMLBCL). Rituximab-CHOP (R-CHOP) is the standard of care for diffuse large B-cell lymphoma, whereas efficacy in PMLBCL has not been adequately confirmed.Patient and Methods.: Seventy-six consecutive PMLBCL patients who received R-CHOP with or without radiotherapy (RT) were compared with 45 consecutive historical controls treated with CHOP with or without RT. Baseline characteristics of the two groups were balanced.Results.: The rate of early treatment failure was much lower with R-CHOP with or without RT (9% versus 30%; p = .004). The 5-year freedom from progression rate after R-CHOP with or without RT was 81%, versus 48% for CHOP with or without RT (p < .0001). The 5-year event-free survival rates were 80% and 47% (p < .0001) and the 5-year overall and lymphoma-specific survival rates were 89% and 69% (p = .003) and 91% and 69% (p = .001), respectively, with only seven of 76 lymphoma-related deaths. Among R-CHOP responders, 52 of 68 received RT.Conclusions.: Based on these results, most patients with PMLBCL appear to be cured by R-CHOP in 21-day cycles with or without RT, which could be the current standard of care. Therefore, the need for more aggressive treatment strategies is questionable unless high-risk patients are adequately defined. Further studies are required to establish the precise role of RT.

Purpose: Activation of phosphatidylinositol 3′-kinase pathway is implicated in the pathogenesis of mantle cell lymphoma (MCL). The genetic change in phosphatidylinositol 3′-kinase catalytic subunit α (PIK3CA) in MCL has not been identified.