De novo acute B cell leukemia/lymphoma with t(14;18)

Abstract

The t(14;18)(q32;q21) translocation is the most common translocation in B cell malignancies being found in 80% of follicular lymphomas and about 20% of diffuse large B cell lymphomas. Only rare cases of de novo acute B cell lymphoblastic leukemia with t(14;18) have been described. We describe five cases of this entity which appears to have very homogeneous clinical, phenotypic and genotypic features. None of these patients had prior history of follicular lymphoma. The disease was characterized by acute clinical features with nodal and/or extranodal disease, massive bone marrow infiltration and rapid increase of circulating blast cells of mature B cell phenotype. All patients disclosed complex chromosomal and molecular abnormalities involving at least the BCL-2 and c-MYC genes. Furthermore, three patients had evidence of BCL-6 involvement and one patient had a p53 mutation. Despite intensive chemotherapy, including for two patients allogeneic bone marrow transplantation in first complete remission, all patients died within a few months. Neuro-meningeal relapse occurred in three of the five patients in spite of neuro-meningeal prophylaxis. De novo leukemia/lymphoma with t(14;18) is a rare entity with a very poor prognosis. Whether early bone marrow transplant could modify the natural history of the disease remains to be determined. An intensive neuro-meningeal prophylaxis appears to be mandatory in these patients. Leukemia (2000Leukemia ( ) 14, 1960Leukemia ( -1966

Concurrent translocation of BCL2 and MYC with a single immunoglobulin locus in high-grade B-cell lymphomas

“…16,[19][20][21][22][23][24] The molecular structure of the t(8;14;18) rearrangement has been studied in detail in the cell lines DOHH2, VAL and ROS-50. 5 These studies have demonstrated that concurrent deregulation of BCL2 and MYC was achieved by translocation with a single IGH allele, whereby separation of the 3 0 and 5 0 IGH enhancer elements occurs with relocation of the BCL2-5 0 IGH enhancer fusion to the der (8), and translocation of MYC adjacent to the 3 0 IGH enhancer element that is retained on the der (14).…”

Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia

“…4 High expression of Bcl-2, an anti-apoptotic protein, can be associated with drug resistance in hematological malignancies. 4,11,[36][37][38][39][40][41][42][43][44][45][46][47] Thus, even the lower expression of Bcl-2 in some samples could provide an optimal anti-apoptotic effect. The role of Bcl-2 as a prognostic indicator remains controversial and it has therefore been suggested that Bcl-2 should be evaluated in parallel with other apoptotic markers.…”

Suppression of apoptosis: role in cell growth and neoplasia

“…81 The importance of the Bcl-2 family of proteins is underscored by reports of their dysregulation in many hematological malignancies that can contribute to the resistance of such malignancies to pro-apoptotic chemotherapeutic drugs. [82][83][84][85][86][87][88][89][90] Apoptosis due to the cell receiving an abnormal proliferative signal…”