scholarly journals γδ T-Cell Acute Lymphoblastic Leukemia/Lymphoma: Discussion of Two Pediatric Cases and Its Distinction from Other Mature γδ T-Cell Malignancies

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Eric X. Wei ◽  
Vasiliki Leventaki ◽  
John K. Choi ◽  
Susana C. Raimondi ◽  
Elizabeth M. Azzato ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
White Cell Count ◽  
Flow Cytometric Analysis ◽  
Molecular Diagnostic ◽  
Allogeneic Bone ◽  
Γδ T Cell ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Cellular Markers

Gamma delta (γδ) T-cell antigen receptor (TCR) expression and its related T-cell differentiation are not commonly reported in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL). Here we report two pediatric T-ALL cases and present their clinical features, histology, immunophenotypes, cytogenetics, and molecular diagnostic findings. The first patient is a two-year-old girl with leukocytosis, circulating lymphoblasts, and a cryptic insertion of a short-arm segment at 10p12 into the long-arm segment of 11q23 resulting in an MLL and AF10 fusion transcript, which may be the first reported in γδ T-ALL. She responded to the chemotherapy protocol poorly and had persistent diseases. Following an allogeneic bone marrow transplant, she went into remission. The second patient is an eleven-year-old boy with a normal white cell count, circulating blasts, and a normal karyotype, but without any immature cellular markers by flow cytometric analysis. He responded to the chemotherapy well and achieved a complete remission. These cases demonstrate the diverse phenotypic, cytogenetic, and molecular aspects of γδ T-ALL. Early T-precursor- (ETP-) ALL and their differential diagnosis from other mature γδ T-cell leukemia/lymphomas are also discussed.

scholarly journals 583 Exploring the potential of T cell acute lymphoblastic leukemia (T-ALL) for generating leukemia-specific T cell responses that can be therapeutically harnessed with immunotherapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A613-A613
Author(s):  
Todd Triplett ◽  
Joshua Rios ◽  
Alexander Somma ◽  
Sarah Church ◽  
Khrystyna North ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Lymphoblastic Leukemia ◽  
Systemic Disease ◽  
Flow Cytometric Analysis ◽  
T Cell Responses ◽  
Lymphoid Tissues ◽  
Cell Responses ◽  
Cell Acute Lymphoblastic Leukemia

BackgroundT cell Acute Lymphoblastic Leukemia (T-ALL) is a devastating malignancy found primarily in pediatric populations. Unfortunately, standard of care for T-ALL has not progressed from highly toxic, intensive regimens of chemotherapy, which fails to cure all patients. Immunotherapies designed to activate patients‘ leukemia-specific T cells may provide a new therapeutic avenue to increase complete response rates, reduce toxicity without the need to engineer (e.g. CAR) cells. However, it is unknown whether T-ALL is capable of being recognized by T cells due given its relatively low mutation-rate. These studies therefore sought to investigate whether signs of leukemia-specific T cell responses are generated by T-ALL. Because T-ALL results in systemic disease and infiltrates multiple lymphoid and non-lymphoid tissues, these studies also determined how the divergent immune contextures of these TMEs impacts T cell responses to T-ALL. From this, we aim to identify immunotherapeutic targets capable of activating T cells across tissues to eradicate leukemia systemically.MethodsPrimary leukemia cells isolated from a spontaneous murine model (LN3 mice) into immune-competent, congenic (CD45.1) recipient mice. Tissues were harvested at distinct stages of disease for analysis by flow cytometry or utilizing NanoString Technologies’ GeoMX Digital Spatial Profiling (DSP) platform.ResultsFlow cytometric analysis of T cells revealed extensive changes in response to T-ALL that included multiple features of exhaustion typically associated with anti-tumor responses as determined by upregulation of co-inhibitory receptors and TOX. This included a surprisingly high-frequency of PD1+ T cells, which was accompanied by PDL1- and PDL2-expressing myeloid cells that likely are restraining these subsets. Importantly, combination immunotherapy with OX40 agonists while inhibiting PD1 resulted in drastically reduced tumor burden and concomitant expansion of proliferating granzyme-expressing CD8 T cells. To gain better insight into T cell responses within distinct organs, we analyzed tissue sections using DSP. This technique enabled us to evaluate T cells in direct contact with leukemia infiltrates compared to T cells in regions without T-ALL, which further revealed an enrichment of activated subsets. Importantly, these studies have provided critical insight needed to better understand how T cells responding to T-ALL diverge between distinct types of tissues.ConclusionsThe results from these studies collectively suggest that T cells are activated by T-ALL and that they can be therapeutically harnessed despite relatively low mutation-rates. Future studies will continue analysis of individual organs and use these results to rationally design combinations of immunotherapies by tailoring to activate T cells in all tissue types.AcknowledgementsSpecial thanks to all the support and analysis from everyone at NanoString, along with financial support provided by a SITC-NanoString DSP Fellowship awarded to Dr. Todd Triplett used for DSP analysis of all frozen tissues in these studies. Salary support for Dr. Triplett and pilot funding was provided by departmental funds via a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar Award (Grant #RR160093; awarded to Dr. Gail Eckhardt).

How could improvement in the management of T-cell acute lymphoblastic leukemia be achieved? Experience of Princess Nourah Oncology Center, National Guard Hospital, Jeddah, Saudi Arabia

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10048-10048
Author(s):  
T. M. Khattab ◽  
W. A. Jastaniah ◽  
S. K. Felimban ◽  
N. Elemam ◽  
K. Abdullah ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
National Guard ◽  
Lymphoblastic Leukemia ◽  
White Cell Count ◽  
Tumor Lysis Syndrome ◽  
Risk Classification ◽  
Published Data ◽  
Cell Acute Lymphoblastic Leukemia

10048 Background: T-cell acute lymphoblastic leukemia (T-ALL) is representing 10–15% of pediatric ALL. The use of more intensive treatments and risk adapted therapy have significantly improved the outcome of patients with T-ALL and event-free survival rate of 60–70% are now reported in children. Our published data showed that T-ALL phenotype patients fared poorly with 5 year survival of 27% versus 83% for precursor B-ALL (Recent Advances Research Update: 2006, 7; 1, P 51–56). Objectives: We reviewed all patients diagnosed with T-ALL to assess risk classification according to NCI criteria, type of therapy received, overall survival and causes of mortality. Methods: Retrospective review of all patients files diagnosed with T-ALL from 1989 until now with data collection including; sex, age, white cell count (WBCs), CNS disease, type of protocol used, length of survival, overall survival, cause of death (toxic, disease). Results: Over the last 20 years, T-ALL cases registered were 52/460 (11%) of all ALL cases, Male:Female ratio 42:10 (4.2:1), median age 7 year (range: 1.5–12 yrs). Median WBCs 50,000/Cmm (range: 1.500–619,000/Cmm) and positive CNS at diagnosis 10/52 (20%). NCI risk classification criteria showed SR 24/52 (46%) and HR 28/52 (54%). Protocols used were UKALL ( n = 21; 3 UKALL X-B, 4 UKALL X-D, 10 UKALL XI and 4 MRC-97 ). BFM (n = 8); and CCG 1961 (n = 23). Overall survival 27/52 (52%) and 25 pts. died (48%); 15 secondary to disease recurrence (9 on UKALL, 4 BFM, 2 CCG 1961); 4 during induction, 1 fulminant hepatic failure, 1 tumor lysis syndrome, and 4 due to toxicities (mucormycosis, staphylococcal toxic shock syndrome, CMV pneumonia, pseudomonas sepsis). Survival for different regimen; UKALL: 5/21=31%, BFM: 4/8=50%, CCG: 18/23=78%, while overall cohort survival 52%. Mean length of survivors 4 year (range 4–140 month) and mean length for non-survivors 1 year (range 0.1–40 months). Conclusions: This review showed the improvement of T-ALL survival from 27% to 56%. Using augmented therapy based on CCG1961 was associated with better outcome. Further risk and response stratification in addition to intensification of therapy for T-cell ALL in our center may prove to be beneficial. Therapy remains an important prognostic factor. No significant financial relationships to disclose.

Hepatosplenic γδ T-Cell Lymphoma Masquerading as T Cell Acute Lymphoblastic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5310-5310
Author(s):  
Kunal Sehgal ◽  
P. G. Subramanian ◽  
Prashant Tembhare ◽  
Y. Badrinath ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Tumor Cells ◽  
Peripheral Blood ◽  
Cell Lymphoma ◽  
Lymphoblastic Leukemia ◽  
Γδ T Cell ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Antibody Panel ◽  
Isochromosome 7Q

Abstract Hepatosplenic γδ T-Cell Lymphoma (HSTCL) is an uncommon type of Peripheral T cell lymphomas characterized by hepatosplenomegaly without significant lymphadenopathy, with clinically significant cytopenias, predominance in young adult males and an aggressive clinical course. HSTCL have a characteristic immunophenotype CD2+, CD3+, CD4−, CD5−, CD7+, CD8-, TCRγδ+ and are associated with isochromosome 7q cytogenetic abnormality. The predominant laboratory findings are reduced peripheral blood cells ranging from isolated reduction of one lineage to pancytopenia. Lymphocytosis is usually uncommon at the point of diagnosis; however tumor cells may be commonly seen in blood. Two subpopulations of atypical cells are seen – small sized cells with irregular nuclear margins and the medium to large size cells which often resemble blasts. The blast like cells are known to increase with disease progression and a complete blastic transformation though known has been mostly reported in the terminal phase of the disease. We present three cases of HSTCL, all of which presented with lymphocytosis and increased blast like cells (17%–91%) at diagnosis. These cases included two females and one male in an age group of 13– 17 years. They all presented with generalized systemic complaints, bleeding symptoms and on examination had pedal edema, facial puffiness and moderate to marked hepatosplenomegaly. Immunophenotyping performed on peripheral blood sample using a limited primary panel of antibodies showed a common phenotype: surface CD3+, CD4−, CD8−, CD7+ & CD34−. In addition CD2 and CD5 were positive in two cases, CD56 was positive in one case while CD16 was negative in all three cases. Based on the blast like morphology of tumor cells and an aberrant T cell phenotype, all three cases were initially labeled as T cell Acute Lymphoblastic Leukemia (T-ALL) and treated as per the T-ALL treatment protocol of our institute. However they did not respond to treatment. These cases were reviewed in detail and a repeat Immunophenotypic analysis was done using a more elaborate panel. In addition to the initial Immunophenotypic markers, all three cases were positive for Surface TCR γδ and negative for Tdt. Hence a diagnosis of HSTCL was arrived at. Cytogenetically only one case showed the characteristic finding of isochromosome 7q. The diagnosis of HSTCL was not considered initially because of the blast like morphology of tumor cells and as surface TCR αβ/γδ is not part of our primary antibody panel. In addition in one case, cytoplasmic CD3 was interpreted as positive without taking into account surface CD3 positivity. This case series highlights the importance of using a comprehensive antibody panel for the diagnosis of hematolymphoid neoplasms including cytoplasmic markers and Tdt. It re-establishes the importance of assessing cytoplasmic positivity only after the surface positivity has been looked for. Aberrant surface CD3 expression and cytoplasmic γδ positivity is well known in T-ALL and a few cases of Tdt negative T-ALL are also known. However to the best of our knowledge there are no published reports of T-ALL expressing surface TCR γδ and in comparison HSTCL though surface CD3 positive, are Tdt negative. We suggest that in all such cases which are surface CD3 positive, CD34 negative and Tdt negative, Surface TCR γδ should be looked for and if found to be positive a diagnosis of HSTCL can be arrived at in the correct clinical setting. In conclusion, it is important to be aware of this rare entity of HSTCL presenting with leucocytosis & blast like cells and to differentiate it from T-ALL, as these two entities have different treatment and prognosis.

scholarly journals Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Terrie Flatt ◽  
Kathleen Neville ◽  
Karen Lewing ◽  
Jignesh Dalal
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Bone Marrow Transplant ◽  
Fanconi Anemia ◽  
Lymphoblastic Leukemia ◽  
Marrow Transplant ◽  
Allogeneic Bone ◽  
Increased Risk ◽  
Cell Acute Lymphoblastic Leukemia

Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.

scholarly journals Inhibition of BCL11B induces downregulation of PTK7 and results in growth retardation and apoptosis in T-cell acute lymphoblastic leukemia

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Kehan Li ◽  
Cunte Chen ◽  
Rili Gao ◽  
Xibao Yu ◽  
Youxue Huang ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Growth Retardation ◽  
Lymphoblastic Leukemia ◽  
Downstream Target ◽  
B Cell Leukemia ◽  
Cell Acute Lymphoblastic Leukemia ◽  
Induced Apoptosis ◽  
Necrosis Factor ◽  
Aggressive Subtype

AbstractT-cell acute lymphoblastic leukemia (T-ALL) is an aggressive subtype of leukemia with poor prognosis, and biomarkers and novel therapeutic targets are urgently needed for this disease. Our previous studies have found that inhibition of the B-cell leukemia/lymphoma 11B (BCL11B) gene could significantly promote the apoptosis and growth retardation of T-ALL cells, but the molecular mechanism underlying this effect remains unclear. This study intends to investigate genes downstream of BCL11B and further explore its function in T-ALL cells. We found that PTK7 was a potential downstream target of BCL11B in T-ALL. Compared with the healthy individuals (HIs), PTK7 was overexpressed in T-ALL cells, and BCL11B expression was positively correlated with PTK7 expression. Importantly, BCL11B knockdown reduced PTK7 expression in T-ALL cells. Similar to the effects of BCL11B silencing, downregulation of PTK7 inhibited cell proliferation and induced apoptosis in Molt-4 cells via up-regulating the expression of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and p27. Altogether, our studies suggest that PTK7 is a potential downstream target of BCL11B, and downregulation of PTK7 expression via inhibition of the BCL11B pathway induces growth retardation and apoptosis in T-ALL cells.

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