scholarly journals A Chinese Child Presented with Early T Cell Precursor Lymphoblastic Lymphoma

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Xiangyang Pu ◽  
Shengyong Deng ◽  
Nange Yin ◽  
Lin Song ◽  
Xiangling He ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Disease Onset ◽  
Lymphoblastic Lymphoma ◽  
Intensive Chemotherapy ◽  
Cell Precursor ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Leukemic Phase ◽  
Differentiation Stage

T cell lymphoblastic lymphoma (T-LBL) is regarded as the leukemic phase of T cell acute lymphoblastic leukemia (T-ALL). The early T cell precursors ALL/LBL (ETP-LBL/ALL) are derived from thymic cells at the ETP differentiation stage and recognized as a high-risk subgroup of T-ALL/LBL. Most of these cases presented with ALL at the disease onset, but the ETP-LBL phase is uncommon. Here, we report a patient who presented with ETP-LBL at the disease onset. In this case, ALL developed even despite receiving chemotherapy, but the patient achieved a complete remission with intensive chemotherapy.

scholarly journals Deletion of Pten in CD45-expressing cells leads to development of T-cell lymphoblastic lymphoma but not myeloid malignancies

Blood ◽  
2016 ◽  
Vol 127 (15) ◽  
pp. 1907-1911 ◽  
Author(s):  
Cristina Mirantes ◽  
Maria Alba Dosil ◽  
David Hills ◽  
Jian Yang ◽  
Núria Eritja ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Mouse Model ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Cells ◽  
Hematologic Malignancies ◽  
Lymphoblastic Lymphoma ◽  
Key Points ◽  
Pten Deletion ◽  
Cell Acute Lymphoblastic Leukemia

Key Points CD45-driven expression of Cre generates the first mouse model that allows specific and exclusive deletion of Pten in hematopoietic cells. Pten deletion in CD45-expressing cells causes T-cell acute lymphoblastic leukemia, but no other hematologic malignancies.

Frequency of NUP214-ABL1 Oncogene in Patients with T-Cell Acute Lymphoblastic Leukemia (T-ALL) and Analysis of the Activity of Imatinib and Nilotinib in NUP214-ABL1-Expressing T-ALL Cell Lines.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 710-710
Author(s):  
Alfonso Quintas-Cardama ◽  
Weigang Tong ◽  
Taghi Manshouri ◽  
Jan Cools ◽  
D. Gary Gilliland ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Cell Lines ◽  
Inhibitory Activity ◽  
Lymphoblastic Leukemia ◽  
Fusion Transcript ◽  
Lymphoblastic Lymphoma ◽  
Abl Kinase ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Kinase Inhibitory Activity

Abstract The fusion of ABL1 with BCR results in the hybrid BCR-ABL1 oncogene that encodes the constitutively active Bcr-Abl tyrosine kinase encountered in the majority of patients with chronic myeloid leukemia (CML) and in approximately 30% of pts with B-cell acute lymphoblastic leukemia (B-ALL). Recently, the episomal amplification of ABL1 has been described in 6% of pts with T-ALL (Nat Genet2004;36:1084–9). Molecular analysis demonstrated the oncogenic fusion of ABL1 with the nuclear pore complex protein NUP214 (NUP214-ABL1). We screened 29 pts with T-cell lymphoblastic lymphoma (T-LBL) and T-ALL for the presence of the NUP214-ABL1 fusion transcript by RT-PCR using specific primers for the 5 different transcripts thus far described. Three (10%) pts were found to express this fusion transcript, including 2 with T lymphoblastic lymphoma (NUP214 exon 31) and 1 with T-ALL (NUP214 exon 29). This was confirmed by direct sequencing in all cases. All pts received therapy with hyperCVAD and achieved a complete remission (CR). However, 2 of them died 6 and 9 months into therapy, respectively. One other pt remains in CR (19+ months) by morphologic and flow cytometry criteria. However, NUP214-ABL1 is still detectable in peripheral blood by nested PCR, thus suggesting minimal residual disease (MRD). We then studied the activity of the tyrosine kinase inhibitors imatinib and nilotinib in the NUP214-ABL1-expressing cell lines PEER and BE-13. Although PEER and BE-13 cell viability was reduced with both agents, the IC50 was almost 10-fold higher for imatinib (643 nM) than for nilotinib (68 nM) (F test, p<0.001), which parallels the 10− to 30− fold higher Abl kinase inhibitory activity of nilotinib compared to imatinib in BCR-ABL-expressing cells. Nilotinib also potently inhibited the cell proliferation of BE-13 cells (IC50 131 nM). In contrast, Jurkat cells, a T-ALL cell line which does not carry NUP214-ABL1, were remarkably resistant to both imatinib and nilotinib with an IC50 values greater than 5 μM indicating that the cytotoxicity mediated by both TKIs is not related to a general toxic effect on T-ALL cell lines. The inhibition of cellular proliferation by imatinib and nilotinib was associated with a dose- and time-dependent induction of apoptosis in both PEER and BE-13 cells. In Western blotting, higher inhibition of phospho-Abl and phospho-CRKL (a surrogate of Bcr-Abl kinase status) was observed in PEER cells upon exposure to nilotinib as compared with imatinib at their respective IC50 concentrations for cell growth inhibition. We conclude that NUP214-ABL1 can be detected in 10% of pts with T-cell malignancies and its detection can be used as a sensitive marker of MRD. Imatinib and nilotinib potently inhibits the growth of NUP214-ABL1-expressing cells. Given the higher Abl kinase inhibitory activity of nilotinib with respect to imatinib, this agent must be further investigated in clinical studies targeting patients with T-ALL and T-LBL expressing the NUP214-ABL1 fusion kinase.

MEF2C as Novel Oncogene for Early T-Cell Precursor (ETP) Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 9-9
Author(s):  
Irene Homminga ◽  
Rob Pieters ◽  
Anton Langerak ◽  
Johan de Rooi ◽  
Andrew Stubbs ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
Molecular Cytogenetic ◽  
Oncogenic Pathways ◽  
Cytogenetic Analyses ◽  
Cell Acute Lymphoblastic Leukemia

Abstract Abstract 9 To identify novel oncogenic pathways in T-cell acute lymphoblastic leukemia (T-ALL), we combined expression profiling of 117 pediatric patient samples and detailed molecular cytogenetic analyses. Using unsupervised and supervised analyses, we identified a T-ALL cluster that was associated with an immature immunophenotype (CD1−, CD4−, CD8−), frequent expression of CD34 and co-expression of the myeloid markers CD13/CD33. Patients in this cluster lacked any of the known oncogenic rearrangements, but ectopically expressed MEF2C, which was recently demonstrated as an important transcription factor for T-cell development1. Molecular-cytogenetic analyses including the Chromatine Conformation Capture on Chip (4C) method revealed novel rearrangements of the MEF2C locus at 5q14, rearrangement of transcription factors that target MEF2C (PU.1, NKX2-5, RUNX1) or MEF2C-associated cofactors (NCOA2/GRIP1) in about half of the patients in this cluster. Four out of the 6 rearrangements identified have never been observed before in human cancer. Nearly all of these patients in this cluster could be predicted by the early T-cell precursor (ETP) signature2 using PAM statistics. This indicates that MEF2C may represent the oncogene for ETP T-ALL, an entity that has been associated with poor outcome2. Inhibition of MEF2C in a cell line model system provoked relieve of developmental arrest, indicating that ectopic MEF2C expression blocks T-cell development at an early stage. We demonstrated that MEF2C is a transcriptional regulator for many differentially expressed genes that were associated with the immature cluster including LYL1 and LMO2. Although LYL1 has been suggested as potential oncogene for immature T-ALL cases3, oncogenic rearrangements were never identified in T-ALL cases with immature immunophenotype. Our data therefore imply that high expression of LYL1 (and LMO2) is part of a pathogenic pathway for immature T-ALL that is regulated by the MEF2C oncogene. 1 Stehling-Sun, S., Dade, J., Nutt, S. L., DeKoter, R. P. & Camargo, F. D. Regulation of lymphoid versus myeloid fate ’choice’ by the transcription factor Mef2c. Nat Immunol 10, 289–296, (2009). 2 Coustan-Smith, E. et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 10, 147–156, (2009). 3 Ferrando, A. A. et al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 1, 75–87 (2002). Disclosures: No relevant conflicts of interest to declare.

scholarly journals How I treat newly diagnosed T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in children

Blood ◽  
2020 ◽  
Vol 135 (3) ◽  
pp. 159-166 ◽  
Author(s):  
David T. Teachey ◽  
David O’Connor
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Current Treatment ◽  
Lymphoblastic Lymphoma ◽  
Cooperative Groups ◽  
Cranial Radiotherapy ◽  
Treatment Protocols ◽  
Cell Acute Lymphoblastic Leukemia

Abstract T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy that has historically been associated with a very poor prognosis. Nevertheless, despite a lack of incorporation of novel agents, the development of intensified T-ALL–focused protocols has resulted in significant improvements in outcome in children. Through the use of several representative cases, we highlight the key changes that have driven these advances including asparaginase intensification, the use of induction dexamethasone, and the safe omission of cranial radiotherapy. We discuss the results of recent trials to explore key topics including the implementation of risk stratification with minimal residual disease measurement and how to treat high-risk subtypes such as early T-cell precursor ALL. In particular, we address current discrepancies in treatment between different cooperative groups, including the use of nelarabine, and provide rationales for current treatment protocols for both T-ALL and T-lymphoblastic lymphoma.

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