Case of acute lymphoblastic leukemia presenting with t(14;18)/BCL2, t(8;14)/cMYC, and t(1;2)/FCGR2B

Abstract

The majority of follicular lymphoma and Burkitt's lymphoma are associated with reciprocal translocations involving BCL2 and cMYC, respectively. Unusual reports of aggressive lymphoma presenting with both translocations have been described as well as rare cases with a third structural alteration usually involving BCL6. The patient described here presented with aggressive high-grade lymphocytic leukemia, FAB subtype L2 (ALL-L2), and three reciprocal translocations, t(14;18)(q32;q21), t(8;14)(q24.1;q32), and t(1;2) (q22-23;p13). Despite immature morphology the leukemic blasts had a mature B-cell phenotype; they were positive for surface immunoglobulin heavy chains and negative for CD34, TdT, and CD10. Most reported dual t(14;18)/t(8;14) cases have not shown sIg and were positive for CD10. Molecular genetic analyses showed the typical rearrangements of BCL2 and cMYC as well as the FCGR2B gene on chromosome 1q23. The occurrence of a third oncogene rearrangement in association with the dual BCL2, cMYC translocations in ALL patients is very rare. To our knowledge, this is the first case where the third hit involves the FCGR2B locus. This report reiterates the poor prognosis associated with activation of cMYC together with elevated Bcl-2 expression. These data also support recent evidence that dysregulation of FCGR2B may play a role in tumor progression.

C-MYCtranslocation in t(14;18) positive follicular lymphoma at presentation: An adverse prognostic indicator?

“…Clonal rearrangement of C-MYC is the cytogenetic hallmark of Burkitt's lymphoma, and is also encountered in other high grade haematological malignancies, including DLBCL [12 -15], and acute lymphoblastic leukemia [16,17]. In these situations, t(8;14)(q24;q32) is the most common translocation, but t(2;8)(p12;q24) and t(8;22) (q24;q11) variants are sometimes encountered [18].…”

Presence of somatic hypermutation and activation‐induced cytidine deaminase in acute lymphoblastic leukemia L2 with t(14;18)(q32;q21)

“…There is expression of double light chain isotype in this case (58.7% and >90% for κ and λ , respectively), as have been reported in leukemia, lymphoma, and myeloma cases (43–45). The other one case (18) included in Table 4, showing such double light chain isotype. How characteristic is this transitional phase type of dual light chain expression in the κ – κ λ – λ pathway (46–48) in ALL with t(14;18), remains unknown.…”

“…ALL cases with t(14;18)(q32;q21) often show additional chromosomal translocation involving 8q24 or c‐myc gene rearrangement by Southern blot analysis. So far, 28 cases of ALL with t(14;18) have been reported, of which nine cases (32%) showed c‐myc gene rearrangement (4, 7, 8, 14, 16, 18). Particularly in ALL‐L2 with t(14;18), the coexistence of t(8;14)(q24;q32), t(2;8)(p11;q24), or t(8;22)(q24;q11) has been reported in four of 11 (36%) cases so far (Table 4); 380 is the only cell line reported with this feature (4).…”

A Highly Therapy-Resistant Case of B-Cell Lymphoma, Unclassifiable, with Features Intermediate between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma Showing Strong BCL2 Staining, Otherwise Indistinguishable from Burkitt Lymphoma

“…2f) did not suggest lymphoblastic lymphoma. 5 The clinical stage (CS) was defined as CS IV according to the modified Ann Arbor staging system. After chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), a modified LMB regimen containing highdose methotrexate (MTX), cyclophosphamide, and cytarabine was performed.…”