scholarly journals Prevalence of early T-cell precursor acute lymphoblastic leukemia among immunophenotypically categorised acute T-cell lymphoblastic leukaemia cases

2021 ◽  
Author(s):  
Monika Gupta ◽  
Pinki Devi ◽  
Anjali Bishley ◽  
Sant Prakash Kataria ◽  
Rajeev Sen
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Acute Lymphoblastic Leukaemia ◽  
B Cell ◽  
Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukemia ◽  
Cell Lineage ◽  
Cell Precursor ◽  
Cell Markers

Acute lymphoblastic leukaemia is the most common hematopoietic malignancy in childhood, comprising of B-cell lineage (85%) and T-cell lineage (15%). Recent studies have identified a subtype of T-cell acute lymphoblastic leukaemia (T-ALL) termed “early T-cell precursors (ETP)” recognised as a new provisional entity in 2016 update to the World Health Organization (WHO) classification of acute leukaemia, early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is characterized by a unique immunophenotype and genetic profile and its origin has been found to be from migration of cells from thymus to bone marrow. Hence, our study aims at reporting the prevalence of ETP-ALL among immunophenotypically categorised acute T-cell lymphoblastic leukaemia cases. Present work is a retrospective observation of acute T-cell lymphoblastic leukemias and reporting ETP-ALL cases seen during the period of over two years (from August 2018 to August 2020) received for flowcytometry in the department of Pathology, PGIMS, Rohtak, Haryana. Peripheral blood showed features of acute leukemia and immunophenotyping was performed. Fourteen cases were received for flowcytometry showing features of acute leukemia and immunophenotyping was performed revealing two ETP-ALL cases with positivity for cytCD3, CD7 (T-cell markers), HLA-DR, CD13 (myeloid marker-aberrant expression), sCD34, CD117 (stem cell markers), CD19 (B-cell marker) and dim expression of CD45. This study is a supportive data for immunophenotypic identification of ETP-ALL cases in centres where genetic study and other ancillary techniques are not available. It needs to be differentiated from non ETP-ALLs as this entity has been reported to show treatment failure with the treatment modalities for non ETP-ALLs.

Clinical Significance of NT5C2 Mutations in Children with First Relapse of B-Cell Precursor Acute Lymphoblastic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3789-3789 ◽  
Author(s):  
Jana Hof ◽  
Annabell Szymansky ◽  
Arend von Stackelberg ◽  
Cornelia Eckert ◽  
Renate Kirschner-Schwabe
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Clinical Significance ◽  
Lymphoblastic Leukemia ◽  
Similar Proportion ◽  
Cell Precursor ◽  
Childhood All ◽  
Relapse Treatment ◽  
First Relapse

Abstract The ubiquitous cytosolic 5´nucleotidase II (NT5C2) dephosphorylates purine nucleotide monophosphates and has an important role in cellular purine metabolism. Increased levels of nucleotidase activity have been correlated with resistance to nucleoside analog drugs that are commonly used in the treatment of children with acute lymphoblastic leukemia (ALL). Recently, activating mutations of NT5C2 have been identified in relapsed childhood ALL. NT5C2 mutations were present in 20% and 10% of children with relapsed T-cell ALL and with relapsed B-cell precursor ALL, respectively. In vitro studies showed that NT5C2 mutations conferred an increased resistance to purine analog drugs to ALL cell lines. However, the predictive and prognostic value of NT5C2 mutations for response and outcome of patients has remained elusive and systematic studies are warranted. Therefore, we studied the presence of NT5C2 mutations in 259 children with first relapse of B-cell precursor ALL. The patient cohort was a representative subset the German relapse trial ALL-REZ BFM 2002. NT5C2 exons 9, 13, 15 and 16 were sequenced according to Sanger in leukemic samples taken at diagnosis of first relapse. The clinical significance of NT5C2 mutations was assessed by comparing clinical parameters and survival differences between patients with and without NT5C2 mutation, and by multivariate Cox regression modelling. We identified NT5C2 mutations in 5.8% (15/259) of patients with first relapse of B-cell precursor ALL. This confirms the overall lower NT5C2 mutation rate in children with relapsed B-cell precursor ALL compared to those with relapsed T-cell ALL. Sixty percent (9/15) of the patients with NT5C2 mutation showed a G to A transition in codon 367 in exon 13. This mutation substitutes arginine with glutamine (p.R367Q) and represents a mutation hot spot in relapsed T-cell ALL. Our study reveals that p.R367Q is the predominant site of mutation also in relapsed ALL of B-cell precursor lineage. Patients with NT5C2 mutation significantly more often presented with a very early relapse within 18 months after initial diagnosis (P<0.001) compared to patients with wildtype NT5C2. Likewise, the median time of first remission was significantly shorter in patients with NT5C2 mutation (1.5 years versus 2.83 years, P<0.001). Regarding outcome after relapse treatment, patients with NT5C2 mutation showed a significantly reduced event-free (0.143±0.094 vs. 0.483±0.032; P=0.003) and overall survival rate (0.284±0.121 vs. 0.569±0.033; P=0.007) compared to patients with wildtype NT5C2. The predominant second event in relapse patients with NT5C2 mutation was the occurrence of a second relapse. Accordingly, the cumulative incidence of second relapse was significantly increased in patients with NT5C2 mutations compared to patients with wildtype NT5C2 (0.643±0.140 vs. 0.302±0.030; P=0.001). Multivariate analysis including time of relapse and site of relapse as established risk stratification factors in relapsed ALL revealed that NT5C2 mutation is an independent predictor for the occurrence of a second relapse (P=0.002). Surprisingly, mutation of NT5C2 was not associated with response to relapse treatment. Response was assessed by histological examination and by PCR-based sensitive detection of minimal residual disease at different time points during treatment. However, patients with NT5C2 mutation showed a similar proportion of responding and non-responding patients than relapsed children with wildtype NT5C2. We conclude that mutation of NT5C2 can serve as predictor for the occurrence of a second relapse independent of response to relapse treatment in children with relapsed B-cell precursor ALL. Disclosures No relevant conflicts of interest to declare.

Characterization of immunoglobulin and T-cell receptor gene patterns in B-cell precursor acute lymphoblastic leukemia of childhood.

1990 ◽  
Vol 8 (3) ◽  
pp. 431-442 ◽  
Author(s):  
C A Felix ◽  
D G Poplack ◽  
G H Reaman ◽  
S M Steinberg ◽  
D E Cole ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukemia ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Leukemic Cells ◽  
Cell Precursor

Immunoglobulin (Ig) and T-cell receptor (TCR) genes were examined in the lymphoblasts of 70 children with immunophenotypically defined B-cell precursor acute lymphoblastic leukemia (ALL). The most frequent genes to rearrange were Ig heavy (H) chain (93%) and TCR delta (79%), followed by TCR gamma (49%), Ig kappa and/or lambda light (L) chain (46%), TCR alpha (46%), and TCR beta (29%). Thus, despite their putative "B-cell precursor" lineage, these leukemias manifest a remarkably high incidence of TCR gene rearrangements. While certain patterns predominate, there is considerable heterogeneity in Ig and TCR genotypes in this disease. No significant associations were found between Ig and TCR genotype and commonly used prognostic factors including age, sex, race, WBC, French-American-British (FAB) subtype, or cytogenetics. However, the lymphoblasts of three of six patients who failed to achieve initial remission had germline patterns of every Ig and TCR gene, a genotype not observed in the leukemic cells from any of the 64 patients who achieved complete remission (p2 = .0007). This study suggests that particular Ig and TCR genotypes may be of clinical relevance in childhood B-cell precursor ALL. The finding of rearranged TCR genes in a large proportion of cases raises fundamental questions about early lineage commitment and lymphocyte differentiation along B-cell and T-cell pathways.

scholarly journals The CD70/CD27 Pathway Is Critical for Stimulation of an Effective Cytotoxic T Cell Response against B Cell Precursor Acute Lymphoblastic Leukemia

2008 ◽  
Vol 182 (1) ◽  
pp. 718-725 ◽  
Author(s):  
Ludmila Glouchkova ◽  
Birgit Ackermann ◽  
Andree Zibert ◽  
Roland Meisel ◽  
Meinolf Siepermann ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Cell Response ◽  
Lymphoblastic Leukemia ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Cell Precursor ◽  
Stimulation Of

scholarly journals Mixed-phenotypic acute leukemia: cytochemically myeloid and phenotypically early T-cell precursor acute lymphoblastic leukemia

2014 ◽  
Vol 49 (3) ◽  
pp. 196 ◽  
Author(s):  
Smeeta Gajendra ◽  
Ritesh Sachdev ◽  
Pranav Dorwal ◽  
Shalini Goel ◽  
Bhawna Jha ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
Acute Leukemia ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor

Developmental process of the T-cell receptor α and δ gene assembly in B-cell precursor acute lymphoblastic leukaemia

1991 ◽  
Vol 78 (2) ◽  
pp. 180-186 ◽  
Author(s):  
Junichi Hara ◽  
Keisei Kawa-Ha ◽  
Yoshihiro Takihara ◽  
Keiko Yumura-Yagi ◽  
Shigehiko Ishihara ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Lymphoblastic Leukaemia ◽  
B Cell ◽  
T Cell Receptor ◽  
Lymphoblastic Leukaemia ◽  
Developmental Process ◽  
Cell Receptor ◽  
Cell Precursor ◽  
Gene Assembly

scholarly journals Concepts in immuno-oncology: tackling B cell malignancies with CD19-directed bispecific T cell engager therapies

2020 ◽  
Vol 99 (10) ◽  
pp. 2215-2229
Author(s):  
Andreas Viardot ◽  
Franco Locatelli ◽  
Julia Stieglmaier ◽  
Faraz Zaman ◽  
Elias Jabbour
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Lymphoblastic Leukemia ◽  
Cell Precursor ◽  
B Cell Malignancies ◽  
T Cell Therapy ◽  
Bispecific T Cell Engager

Abstract The B cell surface antigen CD19 is a target for treating B cell malignancies, such as B cell precursor acute lymphoblastic leukemia and B cell non-Hodgkin lymphoma. The BiTE® immuno-oncology platform includes blinatumomab, which is approved for relapsed/refractory B cell precursor acute lymphoblastic leukemia and B cell precursor acute lymphoblastic leukemia with minimal residual disease. Blinatumomab is also being evaluated in combination with other agents (tyrosine kinase inhibitors, checkpoint inhibitors, and chemotherapy) in various treatment settings, including frontline protocols. An extended half-life BiTE molecule is also under investigation. Patients receiving blinatumomab may experience cytokine release syndrome and neurotoxicity; however, these events may be less frequent and severe than in patients receiving other CD19-targeted immunotherapies, such as chimeric antigen receptor T cell therapy. We review BiTE technology for treating malignancies that express CD19, analyzing the benefits and limitations of this bispecific T cell engager platform from clinical experience with blinatumomab.

scholarly journals Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

2015 ◽  
Vol 04 (02) ◽  
pp. 091-094 ◽  
Author(s):  
Shiek Aejaz Aziz ◽  
Susheel Kumar Sharma ◽  
Iram Sabah ◽  
M Aleem Jan
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
T Cell ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Prognostic Significance ◽  
Age Groups ◽  
Cell Lineage ◽  
Risk Category ◽  
Study Cohort ◽  
Classification Management

Abstract Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL) patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 patients of all age groups were enrolled for the study, of which flow cytometry was done in 144 patients. Statistical Analysis Used: Analysis was done using the variables on SPSS (statistical package for social sciences) software on computer. Survival curves were estimated by method of Kaplan-Meir. Results: Majority of the patients were of B-cell (68.1%) and 30.6% patients were of T-cell lineage. Of these, 80.6% patients were having cALLa positivity. Complete remission (CR) was achieved in 59.1%, 16.4% relapsed, and 20.1% patients died. Conclusions: Phenotyping has become an important and integral part of diagnosis, classification, management and prognosticating in ALL. B-cell has been found to have a better survival over T-cell lymphoblastic leukemia. cALLa antigen positivity has good impact in achieving CR in only B-cell lineage, myeloid coexpression has no significant effect on the outcome. BFM (Berlin-Frankfurt-Münster) based protocols though showed a higher CR and survival vis-a-vis UKALL-XII. However, patients enrolled in former group being of low risk category and lesser in numbers cannot be compared statistically with a fair degree of confidence.

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