First description of the t(10;11)(q22;q23)/MLL-TET1 translocationin a T-cell lymphoblastic lymphoma, with subsequent lineage switchto acute myelomonocytic myeloid leukemia.

Antoine Ittel, Eric Jeandidier, Catherine Helias, Nathalie Perrusson, Catherine Humbrecht, Bruno Lioure, Isabelle Mazurier, Caroline Mayeur-Rousse, Amandine Lavaux, Sylvie Thiebault, Felix Lerintiu, Carine Gervais, Laurent Mauvieux

In the April 2013 issue of Haematologica, Lee et al. have described the TET1 genomic breakpoints and clinical features of MLL-TET1 rearranged cases of acute leukemia. So far, 13 cases have been reported in the literature, 11 in acute myeloid leukemia (AML) patients and 2 in B-cell precursor acute lymphoblastic leukemia (ALL). It was also recently reported that MLL is fused to TET1 in only 5 out of 1,590 MLL rearranged AML cases (0.3%). Although those cases are very uncommon, their study can improve our current understanding of leukemogenesis. We report here the first t(10;11) MLL-TET1 positive case of T-cell lymphoblastic lymphoma occurring in a 31-year old male patient, with a subsequent transformation to AML. The patient was referred for a large mediastinal mass and right pleural effusion. Blood cell count showed no abnormalities. Mediastinal and bronchus biopsies led to the diagnosis of a precursor-T-cell lymphoblastic lymphoma (pre-T LBL), expressing CD3, CD5, CD4, CD8 and CD10 antigens, together with a high expression of Ki67 (90%). No expression of CD34 or CD79a was observed. The same cells were observed in pleural fluid that expressed CD3, CD4, CD8, CD2, CD7, CD10 antigens but neither CD34 nor myeloperoxidase. Bone marrow examination and central nervous system imaging did not show any other specific localization. The patient was treated following the Groupe d’Etudes des Lymphomes de l’Adulte (GELA) LL03 protocol, and was considered in complete remission after induction and consolidation phases. A 32×22×48 mm residual mediastinal mass remained after treatment, without hypermetabolic abnormality on the FDG-PET scan and was considered to be fibronecrotic scar tissue. Fourteen months after the diagnosis, during the maintenance therapy, a bone marrow examination was performed for thrombopenia (6 g/L) that revealed a myelomonocytic acute leukemia with trilineage dysplasia. The mediastinal mass remained unchanged on the imaging scan. The patient achieved complete remission after intensive chemotherapy based on cytarabine and daunorubicin, followed by a consolidation course with high-dose cytarabine. A non-familial donor allogeneic bone marrow transplant (10/10 match) was performed four months after the diagnosis of the acute myeloid leukemia that was complicated by a Grade IV acute graft-versus-host disease involving digestive tract, liver and skin. The patient died 54 days after the transplant of bacterial sepsis leading to multi-organ failure.