An Analysis of Apoptosis and Wnt/Beta Catenin Pathway In The Interaction of Leukemic Cells and Mesenchymal Stem Cells Derived From Bone Marrow of Patients with Childhood Acute Lymphoblastic Leukemia and Healthy Donors

2017 ◽  
Author(s):  
Tuba Ozdemir Sanci
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Beta Catenin ◽  
Healthy Donors

scholarly journals Leukemia-Induced Cellular Senescence and Stemness Alterations in Mesenchymal Stem Cells Are Reversible upon Withdrawal of B-Cell Acute Lymphoblastic Leukemia Cells

2021 ◽  
Vol 22 (15) ◽  
pp. 8166
Author(s):  
Natalia-Del Pilar Vanegas ◽  
Paola Fernanda Ruiz-Aparicio ◽  
Gloria Inés Uribe ◽  
Adriana Linares-Ballesteros ◽  
Jean-Paul Vernot
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Hematopoietic Stem ◽  
Cell Acute Lymphoblastic Leukemia

Leukemic cell growth in the bone marrow (BM) induces a very stressful condition. Mesenchymal stem cells (MSC), a key component of this BM niche, are affected in several ways with unfavorable consequences on hematopoietic stem cells favoring leukemic cells. These alterations in MSC during B-cell acute lymphoblastic leukemia (B-ALL) have not been fully studied. In this work, we have compared the modifications that occur in an in vitro leukemic niche (LN) with those observed in MSC isolated from B-ALL patients. MSC in this LN niche showed features of a senescence process, i.e., altered morphology, increased senescence-associated β-Galactosidase (SA-βGAL) activity, and upregulation of p53 and p21 (without p16 expression), cell-cycle arrest, reduced clonogenicity, and some moderated changes in stemness properties. Importantly, almost all of these features were found in MSC isolated from B-ALL patients. These alterations rendered B-ALL cells susceptible to the chemotherapeutic agent dexamethasone. The senescent process seems to be transient since when leukemic cells are removed, normal MSC morphology is re-established, SA-βGAL expression is diminished, and MSC are capable of re-entering cell cycle. In addition, few cells showed low γH2AX phosphorylation that was reduced to basal levels upon cultivation. The reversibility of the senescent process in MSC must impinge important biological and clinical significance depending on cell interactions in the bone marrow at different stages of disease progression in B-ALL.

scholarly journals Does the Inhibition of Valosin Containing Protein (VCP) Has an Effect on Apoptosis of Bone Marrow Mesenchymal Stem Cells Derived from Acute Lymphoblastic Leukemia Patients and Healthy Donors?

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1576
Author(s):  
Şeyma Kipel ◽  
Hilal Nakkaş ◽  
Sevil Çaylı ◽  
Yasin Köksal ◽  
Habibe Meltem Özgüner
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Acute Lymphoblastic Leukemia ◽  
Cultured Cells ◽  
Lymphoblastic Leukemia ◽  
Data Availability ◽  
Cancer Type ◽  
Healthy Donors ◽  
Cancer Types

Acute lymphoblastic leukemia (ALL) is the most common cancer type observed in childhood. Bone marrow (BM) microenvironment has significant role both at the beginning and the progress of leukemic period. Mesenchymal stem cells (MSCs) that make up microenvironment, regulate growth factors, cytokines and induction of survival of ALL cells by generating intracellular signals and establishing drug resistance. p97/VCP is a type of protein and it is responsible for also intracellular ubiquitin proteasome pathway, endoplasmic-reticulum-associated protein degradation, cell cycle, apoptosis and autophagy. It is shown that p97/VCP is overexpressed in the most of the cancer types including the ALL. p97/VCP inhibitors serve as therapeutic agents. Amongst p97/VCP inhibitors, DBeQ (dibenzylquinazoline-2,4-diamine) provide to undergo apoptosis and prevents cell proliferation. In this study, MSCs obtained from ALL patients and healthy donors were isolated by density-gradient method and then these cells were cultured. Cells were incubated with DBeQ. Cell apoptosis was determined by Annexin V/PI method (in flow cytometry). According to obtained data, availability of p97/VCP inhibitor which was recommended to be used as therapeutic agent in the treatment of other cancer types, in ALL treatment will be evaluated and this study will provide a basis for future studies.

Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 52-58 ◽  
Author(s):  
Elaine Coustan-Smith ◽  
Jose Sancho ◽  
Frederick G. Behm ◽  
Michael L. Hancock ◽  
Bassem I. Razzouk ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Induction Chemotherapy ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cell ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Remission Induction

Abstract Early clearance of leukemic cells is a favorable prognostic indicator in childhood acute lymphoblastic leukemia (ALL). However, identification of residual leukemic cells by their morphologic features is subjective and lacks sensitivity. To improve estimates of leukemia clearance, we applied flow cytometric techniques capable of detecting 1 leukemic cell in 10 000 or more normal cells and prospectively measured residual leukemia in bone marrow samples collected on day 19 of remission-induction chemotherapy from 248 children with newly diagnosed ALL. In 134 samples (54.0%), we identified at least 0.01% leukemic cells (0.01%-< 0.1% in 51 samples [20.6%], 0.1%-< 1% in 36 [14.5%], and ≥ 1% in 47 [19.0%]). Among 110 children treated within a single chemotherapy program, the 5-year mean ± SE cumulative incidence of relapse or failure to achieve remission was 32.2% ± 6.5% for the 59 patients with 0.01% residual leukemic cells or greater on day 19 and 6.0% ± 3.4% for the 51 patients with less than 0.01% leukemic cells (P < .001). The prognostic value of day-19 bone marrow status defined by flow cytometry was superior to that defined by morphologic studies and remained significant after adjustment for other clinical and biologic variables. Lack of detectable leukemic cells on day 19 was more closely associated with relapse-free survival than was lack of detectable residual disease at the end of remission induction (day 46). Thus, approximately half of the children with ALL achieve profound clearance of leukemic cells after 2 to 3 weeks of remission-induction chemotherapy, and these patients have an excellent treatment outcome.

scholarly journals Immunophenotypic Modulation of the Blast Cells in Childhood Acute Lymphoblastic Leukemia Minimal Residual Disease Detection

Folia Medica ◽  
2016 ◽  
Vol 58 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Hasan A. Burnusuzov ◽  
Mariya I. Spasova ◽  
Mariana A. Murdjeva ◽  
Angelina A. Stoyanova ◽  
Ivan N. Mumdziev ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Lymphoblastic Leukemia ◽  
Minimal Residual Disease ◽  
Peripheral Blood ◽  
Residual Disease ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Minimal Residual

AbstractEarly clearance of leukemic cells during induction therapy of childhood acute lymphoblastic leukemia (ALL) is a basis for treatment optimization. Currently, the most widely used methods for the detection of minute residual malignant cells in the bone marrow and/or peripheral blood, minimal residual disease (MRD), are PCR and flow cytometry (FCM). Immunophenotypic modulation (IM) is a well known factor that can hamper the accurate FCM analysis.Aim: To report the IM detected by 8-color FCM during the BFM-type remission induction in 24 consecutive MRD-positive samples of children with B-cell precursor ALL and the possible implications for MRD detection.Patients and methods: Between 2010 and 2012 we prospectively followed up the MRD on days 15 and 33 of induction treatment in bone marrow (BM) samples and on day 8 in peripheral blood (PB). The IM was assessed by comparative analyses of the changes in the mean fluorescence intensity of 7 highly relevant antigens expressed by the leukemic cells and normal B-lymphocytes.Results: IM occurred, to different extents, in all analyzed day 15 BM and in most day 33 BM samples. Statistically significant changes in the MFI-levels of four CDs expressed by the leukemic blasts were observed: downmodulation of CD10, CD19 and CD34 and upmodulation of CD20. No changes in the expression of CD38, CD58 and CD45 were noticed.Conclusions: Measuring the MRD by standardized 8-color flow cytometry helps improve the monitoring of the disease, leading to better therapeutic results. However, the IM of the different antigens expressed by the leukemic blasts should be taken into consideration and cautiously analyzed.

scholarly journals Colony formation in vitro by leukemic cells in acute lymphoblastic leukemia (ALL)

Blood ◽  
1978 ◽  
Vol 52 (4) ◽  
pp. 712-718 ◽  
Author(s):  
SD Smith ◽  
EM Uyeki ◽  
JT Lowman
Keyword(s):  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Bone Marrow Cells ◽  
Lymphoblastic Leukemia ◽  
Lymphoid Cells ◽  
Assay System ◽  
Leukemic Cells ◽  
Specific Cell ◽  
Specific Cell Surface

Abstract An assay system in vitro for the growth of malignant lymphoblastic colony-forming cells (CFC) was established. Growth of malignant myeloblastic CFC has been previously reported, but this is the first report of growth of malignant lymphoblastic CFC. Established assay systems in vitro have been very helpful in elucidating the control of growth and differentiation of both normal and malignant bone marrow cells. Lymphoblastic CFC were grown from the bone marrow aspirates of 20 children with acute lymphoblastic leukemia. Growth of these colonies was established on an agar assay system and maintained in the relative hypoxia (7% oxygen) of a Stulberg chamber. The criteria for malignancy of these colonies was based upon cellular cytochemical staining characteristics, the presence of specific cell surface markers, and the ability of these lymphoid cells to grow without the addition of a lymphoid mitogen. With this technique, specific nutritional requirements and drug sensitivities can be established in vitro, and these data may permit tailoring of individual antileukemic therapy.

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