scholarly journals A colony assay for blast cell progenitors in non-B non-T (common) acute lymphoblastic leukemia

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 823-829
Author(s):  
CA Izaguirre ◽  
J Curtis ◽  
H Messner ◽  
EA McCulloch
Keyword(s):  
Cell Culture ◽  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Proliferative Capacity ◽  
Self Renewal ◽  
Colony Assay ◽  
Blast Cells

A clonal method in cell culture is described that permits the quantitation of blast precursors in common (non-T, non-B) ALL; the method also yields information about progenitor properties, based on analysis of cells in colonies. The technique is identical to that used successfully for normal and malignant B-cell progenitors except that it requires culture at below O2 tension (5%-7%); mononuclear cells from blood or marrow are depleted of T cells and cultured with media conditioned by T cells in the presence of phytohemagglutinin and irradiated T cells. Cultures are incubated for 5–7 days in a moist atmosphere at 5% CO2 and 5%-7% O2. Colonies were obtained from marrow or blood of 16 of 18 ALL patients. Cells in colonies had the same characteristics (E-, slg-, cALL+ and clgM+ or clgM-) as the cells in the patient. By replating pooled colonies, self-renewal of progenitors was shown. The findings are considered in light of a model of leukemic blasts that depicts such populations as lineages maintained by progenitors that either renew themselves or give rise to blast cells with little or no proliferative capacity.

scholarly journals A colony assay for blast cell progenitors in non-B non-T (common) acute lymphoblastic leukemia

Blood ◽  
1981 ◽  
Vol 57 (5) ◽  
pp. 823-829 ◽  
Author(s):  
CA Izaguirre ◽  
J Curtis ◽  
H Messner ◽  
EA McCulloch
Keyword(s):  
Cell Culture ◽  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Proliferative Capacity ◽  
Self Renewal ◽  
Colony Assay ◽  
Blast Cells

Abstract A clonal method in cell culture is described that permits the quantitation of blast precursors in common (non-T, non-B) ALL; the method also yields information about progenitor properties, based on analysis of cells in colonies. The technique is identical to that used successfully for normal and malignant B-cell progenitors except that it requires culture at below O2 tension (5%-7%); mononuclear cells from blood or marrow are depleted of T cells and cultured with media conditioned by T cells in the presence of phytohemagglutinin and irradiated T cells. Cultures are incubated for 5–7 days in a moist atmosphere at 5% CO2 and 5%-7% O2. Colonies were obtained from marrow or blood of 16 of 18 ALL patients. Cells in colonies had the same characteristics (E-, slg-, cALL+ and clgM+ or clgM-) as the cells in the patient. By replating pooled colonies, self-renewal of progenitors was shown. The findings are considered in light of a model of leukemic blasts that depicts such populations as lineages maintained by progenitors that either renew themselves or give rise to blast cells with little or no proliferative capacity.

scholarly journals Increase in polymorphonuclear myeloid-derived suppressor cells and regulatory T-cells in children with B-cell acute lymphoblastic leukemia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmaa M. Zahran ◽  
Azza Shibl ◽  
Amal Rayan ◽  
Mohamed Alaa Eldeen Hassan Mohamed ◽  
Amira M. M. Osman ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Critical Role ◽  
Suppressor Cells ◽  
Healthy Controls ◽  
Blast Cells ◽  
Cell Acute Lymphoblastic Leukemia ◽  
The Impact

AbstractOur study aimed to evaluate the levels of MDSCs and Tregs in pediatric B-cell acute lymphoblastic leukemia (B-ALL), their relation to patients’ clinical and laboratory features, and the impact of these cells on the induction response. This study included 31 pediatric B-ALL patients and 27 healthy controls. All patients were treated according to the protocols of the modified St. Jude Children’s Research Hospital total therapy study XIIIB for ALL. Levels of MDSCs and Tregs were analyzed using flow cytometry. We observed a reduction in the levels of CD4 + T-cells and an increase in both the polymorphonuclear MDSCs (PMN-MDSCs) and Tregs. The frequencies of PMN-MDSCs and Tregs were directly related to the levels of peripheral and bone marrow blast cells and CD34 + cells. Complete postinduction remission was associated with reduced percentages of PMN-MDSCs and Tregs, with the level of PMN-MDCs in this subpopulation approaching that of healthy controls. PMN-MDSCs and Tregs jointly play a critical role in maintaining an immune-suppressive state suitable for B-ALL tumor progression. Thereby, they could be independent predictors of B-ALL progress, and finely targeting both PMN-MDSCs and Tregs may be a promising approach for the treatment of B-ALL.

scholarly journals Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1044-1049 ◽  
Author(s):  
K Oshimi ◽  
T Seto ◽  
Y Oshimi ◽  
M Masuda ◽  
K Okumura ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

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.

scholarly journals Increased lysis of patient CD10-positive leukemic cells by T cells coated with anti-CD3 Fab' antibody cross-linked to anti-CD10 Fab' antibody

Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1044-1049
Author(s):  
K Oshimi ◽  
T Seto ◽  
Y Oshimi ◽  
M Masuda ◽  
K Okumura ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Cytotoxic T Lymphocytes ◽  
Peripheral Blood Mononuclear Cells ◽  
Mononuclear Cells ◽  
Lymphoblastic Leukemia ◽  
Interleukin 2 ◽  
Leukemic Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

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.

scholarly journals Common ALL with pre-B-cell features showing (8;14) and (14;18) chromosome translocations

Blood ◽  
1983 ◽  
Vol 62 (5) ◽  
pp. 1142-1146 ◽  
Author(s):  
GJ Mufti ◽  
TJ Hamblin ◽  
DG Oscier ◽  
S Johnson
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Karyotype Analysis ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Chromosome Translocations ◽  
Blast Cells ◽  
Inguinal Lymphadenopathy

Abstract A 21-yr-old man presented with inguinal lymphadenopathy and splenomegaly. The peripheral blood showed a high blast cell count. The morphological and immunologic features of the blast cells were consistent with the diagnosis of common acute lymphoblastic leukemia (ALL) with 15% pre-B-cells. Banded karyotype analysis of the blood and the marrow cells, using the technique of methotrexate synchronization, revealed the presence of (8;14) and (14;18) chromosome translocations, a finding that has not been previously documented. The significance of these findings is discussed.

scholarly journals Common ALL with pre-B-cell features showing (8;14) and (14;18) chromosome translocations

Blood ◽  
1983 ◽  
Vol 62 (5) ◽  
pp. 1142-1146 ◽  
Author(s):  
GJ Mufti ◽  
TJ Hamblin ◽  
DG Oscier ◽  
S Johnson
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Cell Count ◽  
Peripheral Blood ◽  
Karyotype Analysis ◽  
Lymphoblastic Leukemia ◽  
Blast Cell ◽  
Chromosome Translocations ◽  
Blast Cells ◽  
Inguinal Lymphadenopathy

A 21-yr-old man presented with inguinal lymphadenopathy and splenomegaly. The peripheral blood showed a high blast cell count. The morphological and immunologic features of the blast cells were consistent with the diagnosis of common acute lymphoblastic leukemia (ALL) with 15% pre-B-cells. Banded karyotype analysis of the blood and the marrow cells, using the technique of methotrexate synchronization, revealed the presence of (8;14) and (14;18) chromosome translocations, a finding that has not been previously documented. The significance of these findings is discussed.

Targeting Kinase-activating Genetic Lesions to Improve Therapy of Pediatric Acute Lymphoblastic Leukemia

2018 ◽  
Vol 25 (24) ◽  
pp. 2811-2825 ◽  
Author(s):  
Raffaella Franca ◽  
Natasa K. Kuzelicki ◽  
Claudio Sorio ◽  
Eleonora Toffoletti ◽  
Oksana Montecchini ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Fusion Gene ◽  
Hematologic Malignancy ◽  
Lymphoblastic Leukemia ◽  
Point Of View ◽  
Lymphoid Cells ◽  
Gene Encoding ◽  
Pediatric All ◽  
Blast Cells ◽  
Tk Inhibitors

Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children, characterized by an abnormal proliferation of immature lymphoid cells. Thanks to risk-adapted combination chemotherapy treatments currently used, survival at 5 years has reached 90%. ALL is a heterogeneous disease from a genetic point of view: patients’ lymphoblasts may harbor in fact several chromosomal alterations, some of which have prognostic and therapeutic value. Of particular importance is the translocation t(9;22)(q34;q11.2) that leads to the formation of the BCR-ABL1 fusion gene, encoding a constitutively active chimeric tyrosine kinase (TK): BCR-ABL1 that is present in ~3% of pediatric ALL patients with B-immunophenotype and is associated with a poor outcome. This type of ALL is potentially treatable with specific TK inhibitors, such as imatinib. Recent studies have demonstrated the existence of a subset of BCR-ABL1 like leukemias (~10-15% of Bimmunophenotype ALL), whose blast cells have a gene expression profile similar to that of BCR-ABL1 despite the absence of t(9;22)(q34;q11.2). The precise pathogenesis of BCR-ABL1 like ALL is still to be defined, but they are mainly characterized by the activation of constitutive signal transduction pathways due to chimeric TKs different from BCR-ABL1. BCR-ABL1 like ALL patients represent a group with unfavorable outcome and are not identified by current risk criteria. In this review, we will discuss the design of targeted therapy for patients with BCR-ABL1 like ALL, which could consider TK inhibitors, and discuss innovative approaches suitable to identify the presence of patient’s specific chimeric TK fusion genes, such as targeted locus amplification or proteomic biosensors.

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