scholarly journals Identification of Differentially Expressed Genes Associated with Prognosis of B Acute Lymphoblastic Leukemia

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Idalia Garza-Veloz ◽  
Margarita L. Martinez-Fierro ◽  
Jose Carlos Jaime-Perez ◽  
Karol Carrillo-Sanchez ◽  
Maria Guadalupe Ramos-Del Hoyo ◽  
...  

Background.Acute lymphoblastic leukemia type B (B-ALL) is a neoplastic disorder with high mortality rates. The aim of this study was to validate the expression profile of 45 genes associated with signaling pathways involved in leukemia and to evaluate their association with the prognosis of B-ALL.Methods.219 samples of peripheral blood mononuclear cells obtained from 73 B-ALL patients were studied at diagnosis, four, and eight weeks after starting treatment. Gene expression was analyzed by quantitative real-time polymerase chain reaction.Results.Normalized delta Cq values of 23 genes showed differences between B-ALL and controls at diagnosis time (Pvalues < 0.05). There were significant associations between B-ALL patients relapse/death and the expression levels of IL2RA, SORT1, DEFA1, and FLT3 genes at least in one of the times evaluated (Pvalues < 0.05 and odds ratio ranges: 3.73–27). The association between FLT3 deregulation and relapse/death was a constant in the times studied and their overexpression significantly increased the odds of relapse/death in a range of 3.73 and 6.05 among study population (Pvalues < 0.05).Conclusions.Overexpression of FLT3 and DEFA1 genes retained independent prognostic significance for B-ALL outcome, reflected as increased risks of relapse/death among the study population.

Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 869-872 ◽  
Author(s):  
JW Singer ◽  
A Keating ◽  
R Ramberg ◽  
R McGuffin ◽  
JE Sanders ◽  
...  

Abstract This article describes the course of a patient who received an allogeneic marrow graft from his HLA-identical sister for acute lymphoblastic leukemia in second remission. In the second month after grafting, marrow aspirates showed the presence of 7%-10% lymphoblasts. In addition, cytogenetic examination indicated the persistence of host cells. Thereafter, the patient had morphologically normal marrow examinations, with no evidence for recurrent leukemia. In addition, stable hematopoietic chimerism in both the lymphoid and myeloid cell lines has persisted for over 5 yr. Between 20% and 50% of phytohemagglutinin-stimulated peripheral blood mononuclear cells were host-derived on repeated studies. A marrow sample 4 yr after transplantation was established in long-term culture and produced 2% host granulocyte-macrophage colonies at its inception, but 24% host colonies by week 4. Despite this persistent chimerism, no in vitro or in vivo abnormalities of hematopoiesis have been detected.


Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1267-1276 ◽  
Author(s):  
JJ Hutton ◽  
MS Coleman ◽  
S Moffitt ◽  
MF Greenwood ◽  
P Holland ◽  
...  

Abstract Whether the level of terminal deoxynucleotidyl transferase (TdT) activity in mononuclear cells from bone marrow and peripheral blood has prognostic significance has been analyzed prospectively in 164 children with T and non-T, non-B marked acute lymphoblastic leukemia (ALL). TdT was measured at diagnosis to assess its value as a predictor of duration of remission and length of survival. It was measured repeatedly during remission to assess whether it could predict relapse. Ninety-seven percent of the children achieved a complete remission of their disease, and 40% relapsed during the study. The level of TdT activity in blasts at diagnosis varied 1000-fold from patient to patient. There was no statistically significant relationship between TdT activity in cells at diagnosis and the achievement of complete remission, the duration of remission, or length of survival. TdT activity was significantly increased in the bone marrow of 65% of patients at the time of marrow morphological relapse, but was rarely increased in marrow from patients with isolated testicular or central nervous system relapse. Wide fluctuations in TdT activity were characteristically seen in mononuclear cells from the marrow and peripheral blood of patients with ALL at all stages of their disease. An isolated high value of TdT activity in the bone marrow or peripheral blood cannot be taken as evidence of impending relapse. Quantitative measurements of TdT activity alone on mononuclear cells from bone marrow and peripheral blood are helpful in differential diagnosis, but cannot guide therapy of children with ALL.


Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1044-1049 ◽  
Author(s):  
K Oshimi ◽  
T Seto ◽  
Y Oshimi ◽  
M Masuda ◽  
K Okumura ◽  
...  

Abstract An anti-CD3 Fab' x anti-CD10 Fab' bispecific hybrid F(ab')2 antibody (Ab) was generated. This bispecific Ab had a molecular mass of 100 to 110 Kd, and the capacity to react with both CD3+ T cells and CD10+ acute lymphoblastic leukemia (ALL) cells. We studied whether cytotoxic T lymphocytes (CTLs) could lyse patient CD10+ ALL cells after addition of the bispecific Ab. As effector CTLs, interleukin-2 (IL-2)-stimulated peripheral blood mononuclear cells (PBMCs) and CTL clones were used. When IL-2-stimulated PBMCs were assayed for cytotoxicity to 61Cr- labeled CD10+ ALL cells, their activity was shown to be markedly enhanced by the addition of the bispecific Ab. Most of the CTL clones established lacked cytotoxicity for CD10+ ALL cells, but addition of the bispecific Ab induced a significant level of cytotoxicity. CTLs derived from ALL patients also showed significant cytotoxicity for autologous CD10+ ALL cells after addition of the bispecific Ab. However, this Ab did not affect the cytotoxicity of CTLs when CD10- leukemic cells were used as the targets. These findings suggest that the bispecific Ab can be used for immunotherapy in patients with CD10+ ALL.


2016 ◽  
Vol 49 (2) ◽  
pp. 675-681 ◽  
Author(s):  
María Sánchez-Cuaxospa ◽  
Alejandra Contreras-Ramos ◽  
Erandi Pérez-Figueroa ◽  
Aurora Medina-Sansón ◽  
Elva Jiménez-Hernández ◽  
...  

Blood ◽  
1982 ◽  
Vol 60 (6) ◽  
pp. 1267-1276
Author(s):  
JJ Hutton ◽  
MS Coleman ◽  
S Moffitt ◽  
MF Greenwood ◽  
P Holland ◽  
...  

Whether the level of terminal deoxynucleotidyl transferase (TdT) activity in mononuclear cells from bone marrow and peripheral blood has prognostic significance has been analyzed prospectively in 164 children with T and non-T, non-B marked acute lymphoblastic leukemia (ALL). TdT was measured at diagnosis to assess its value as a predictor of duration of remission and length of survival. It was measured repeatedly during remission to assess whether it could predict relapse. Ninety-seven percent of the children achieved a complete remission of their disease, and 40% relapsed during the study. The level of TdT activity in blasts at diagnosis varied 1000-fold from patient to patient. There was no statistically significant relationship between TdT activity in cells at diagnosis and the achievement of complete remission, the duration of remission, or length of survival. TdT activity was significantly increased in the bone marrow of 65% of patients at the time of marrow morphological relapse, but was rarely increased in marrow from patients with isolated testicular or central nervous system relapse. Wide fluctuations in TdT activity were characteristically seen in mononuclear cells from the marrow and peripheral blood of patients with ALL at all stages of their disease. An isolated high value of TdT activity in the bone marrow or peripheral blood cannot be taken as evidence of impending relapse. Quantitative measurements of TdT activity alone on mononuclear cells from bone marrow and peripheral blood are helpful in differential diagnosis, but cannot guide therapy of children with ALL.


2021 ◽  
Vol 9 (1) ◽  
pp. 12-15
Author(s):  
Maria Altaf ◽  
Saleem Ahmed Khan ◽  
Ayesha Khan ◽  
Ammara Arsalan

Objective: To determine the frequency of two transcripts of BCR-ABL 1 fusion gene (P210 & P190) in acute lymphoblastic leukemia and chronic myelogenous leukemia by reverse transcriptase polymerase chain reaction. Study design: A cross-sectional study. Place and duration of study: The Armed Forces Institute of Pathology (AFIP), Rawalpindi, from December 2012 to January 2014. Methodology: 147 diagnosed patients of CML and ALL were subjected to real time reverse transcriptase polymerase chain reaction. For PCR,2-3ml of venous blood in EDTA was collected .RNA extraction was done by Trizol Reagent LS (MRC, USA) and cDNA was synthesized using reverse transcriptase and gene specific primer. Real time- PCR was done on ABI-7500.The positive samples were identified when fluorescence exceeded threshold limit. Results: Out of 147 samples, 85 were with diagnosis of CML. All of them (100%) showed P210. 58 patients had diagnosis of ALL. Out of these BCR-ABL1 is detected in 11(18.9%) patients. 9(81.8%) expressed P190 whereas P210 was present in 2(18.1%) patients. 4 patients in lymphoid blast phase of CML were identified. 3(75%) of them had PP210 and 1(25%) shows both (P190 & P210) the transcripts. Conclusion: All CML patients expressed P210 transcript whereas ALL patients mostly showed P190. These transcripts expressing specific tyrosine kinase protein have diagnostic as well prognostic significance.


2009 ◽  
Vol 390 (4) ◽  
Author(s):  
Kankana Mukherjee ◽  
Anil K. Chava ◽  
Suman Bandyopadhyay ◽  
Asish Mallick ◽  
Sarmila Chandra ◽  
...  

AbstractEnhanced levels of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2GPs) as disease-associated molecules was reported to act as signaling molecules for promoting survival of lymphoblasts in childhood acute lymphoblastic leukemia (ALL). Here, we searched for potential physiological ligands for Neu5,9Ac2GPs that could be involved in modulating the survival of lymphoblasts. Accordingly, we examined the presence of binding proteins for Neu5,9Ac2GPs on cell lines and primary cells of patients with B- and T-ALL, at presentation of the disease. Peripheral blood mononuclear cells from normal healthy donors and cells from myeloid leukemia patients were used for comparison. Neu5,9Ac2GPs-binding proteins (BPs) were specifically detected on the surface of both T- and B-ALL-lymphoblasts and ALL-cell lines along with the consistent presence of Neu5,9Ac2GPs. The Neu5,9Ac2GPs and BPs also co-localized on the cell surface and interacted specificallyin vitro. Apoptosis of lymphoblasts, induced by serum starvation, was reversed in the presence of purified Neu5,9Ac2GPs due to possible engagement of BPs, and the anti-apoptotic role of this interaction was established. This is the first report of the presence of potential physiological ligands for disease-associated molecules like Neu5,9Ac2GPs, the interaction of which is able to trigger an anti-apoptotic signal conferring a survival advantage to leukemic cells in childhood ALL.


Blood ◽  
1983 ◽  
Vol 62 (4) ◽  
pp. 869-872
Author(s):  
JW Singer ◽  
A Keating ◽  
R Ramberg ◽  
R McGuffin ◽  
JE Sanders ◽  
...  

This article describes the course of a patient who received an allogeneic marrow graft from his HLA-identical sister for acute lymphoblastic leukemia in second remission. In the second month after grafting, marrow aspirates showed the presence of 7%-10% lymphoblasts. In addition, cytogenetic examination indicated the persistence of host cells. Thereafter, the patient had morphologically normal marrow examinations, with no evidence for recurrent leukemia. In addition, stable hematopoietic chimerism in both the lymphoid and myeloid cell lines has persisted for over 5 yr. Between 20% and 50% of phytohemagglutinin-stimulated peripheral blood mononuclear cells were host-derived on repeated studies. A marrow sample 4 yr after transplantation was established in long-term culture and produced 2% host granulocyte-macrophage colonies at its inception, but 24% host colonies by week 4. Despite this persistent chimerism, no in vitro or in vivo abnormalities of hematopoiesis have been detected.


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