Genetic features of B‐cell lymphoblastic lymphoma with TCF3‐PBX1

Abstract

Background Lymphoblastic lymphoma (LBL) and acute lymphoblastic leukemia (ALL) are categorized as the same entity under precursor lymphoid neoplasms in the World Health Organization classification. However, compared to B‐cell ALL, the molecular genetic makeup of B‐cell LBL remains to be understood, mainly due to its rarity. We performed whole exome sequencing (WES) on seven patients with TCF3‐PBX1 ‐positive B‐cell LBL. Methods WES was performed using DNA extracted from tumor specimens and paired blood samples at remission for six patients, and tumor‐only analysis was performed for one patient whose remission sample was not available. For one patient, a relapsed sample was also analyzed. Results KMT2D variants and 6q LOH were found as recurrent alterations. Somatic variants of KMT2D were identified in three of the seven patients. Of note, the two patients with heterozygous nonsense variant of KMT2D were at stage III, without bone marrow infiltration. 6q LOH was also identified in two others, out of the seven patients. The common 6q deleted region of the two patients ranged from 6q12 to 6q16.3. Both patients had bone marrow infiltration. Analysis of recurrent case also revealed that the relapsed clone might be derived from a minor clone of the bone marrow at diagnosis. Conclusion In this study, through WES for seven patients with TCF3‐PBX1 ‐positive B‐LBL, we identified KMT2D mutations and 6q LOH as recurrent alterations. In order to elucidate the relationship between these recurrent alterations and disease specificity or outcomes, further studies comparing with TCF3‐PBX1 ‐positive B‐ALL are required.

B-Lymphoblastic Lymphoma in Children: A Case Series From a Single Institution

“…This is considered an intermediate risk lesion in B-ALL as patients have favorable outcomes with modern, intensified chemotherapy regimens, but is reportedly associated with an increased risk of CNS relapse 8,13–15 . TCF3-PBX1 has been previously reported in several B-LLy patients 16,17 . All patients with TCF3-PBX1 fusion-positive B-LLy in prior studies had Stage III or IV disease, consistent with this group in which both patients had stage IV disease.…”

“…8,[13][14][15] TCF3-PBX1 has been previously reported in several B-LLy patients. 16,17 All patients with TCF3-PBX1 fusion-positive B-LLy in prior studies had Stage III or IV disease, consistent with this group in which both patients had stage IV disease. Of the 9 patients previously described in the literature, 3 patients relapsed, and 2 died of disease.…”

“…All patients with TCF3-PBX1 fusion-positive B-LLy in prior studies had Stage III or IV disease, consistent with this group in which both patients had stage IV disease. Of the 9 patients previously described in the literature, 3 patients relapsed, and 2 died of disease 16,17 . In the group described here, one of the 2 patients with TCF3-PBX1 fusion relapsed.…”

“…Of the 9 patients previously described in the literature, 3 patients relapsed, and 2 died of disease. 16,17 In the group described here, one of the 2 patients with TCF3-PBX1 fusion relapsed. With such a small population, the prognostic significance of TCF3-PBX1 in B-LLy is unknown, but these data raise the question of if this lesion confers an increased risk of relapse.…”

Advances in next-generation sequencing for relapsed pediatric acute lymphoblastic leukemia: current insights and future directions

“…Shirai et al reported that, in this investigation, KMT2D mutations and 6q LOH were found to be recurring changes in seven patients with TCF3–PBX1 -positive B-LBL ( Shirai et al, 2022 ). Additional genetic mutations were found in the relapsed tumor that were not present in the primary tumor, including the 6q LOH.…”