Close interaction with bone marrow mesenchymal stromal cells induces the development of cancer stem cell-like immunophenotype in B cell precursor acute lymphoblastic leukemia cells

Kihira, Kentaro; Chelakkot, Vipin Shankar; Kainuma, H.; Okumura, Yosuke; Tsuboya, Naoki; Okamura, S; Kurihara, Kenzo; Iwamoto, Shotaro; Komada, Yoshihiro; Hori, Hiroki

doi:10.1007/s12185-020-02981-z

Cited by 15 publications

(17 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many recent studies reported mutational and phenotypic changes that induce LSC-like properties, which were supported by BMM [12,13]. These phenotypic changes included upregulation of CD34, CD133, P-glycoprotein and BCRP/ABCG2, as well as downregulation of CD38 [12].…”

Section: Introductionmentioning

confidence: 79%

“…These CSCs were reported in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), but their role in ALL is still unclear [11,12]. Many recent studies reported mutational and phenotypic changes that induce LSC-like properties, which were supported by BMM [12,13]. These phenotypic changes included upregulation of CD34, CD133, P-glycoprotein and BCRP/ABCG2, as well as downregulation of CD38 [12].…”

Section: Introductionmentioning

confidence: 98%

“…A growing body of evidence suggests that leukemia stem cells (LSCs) are a subset of cancer cells that maintain chemo-resistance and relapse [10]. These CSCs were reported in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), but their role in ALL is still unclear [11,12]. Many recent studies reported mutational and phenotypic changes that induce LSC-like properties, which were supported by BMM [12,13].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Role of matrix metalloproteinase MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP-1) in the clinical progression of pediatric acute lymphoblastic leukemia

et al. 2021

View full text Add to dashboard Cite

Background: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed. Methods: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38− cancer stem cells (CSCs) were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, p < 0.001], and CSCs CD34 + CD38 − [1 (0.03-18.6) versus 0.3 (0.01-1.1), p < 0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, area under curve (AUC) of MMP-2 were (80.3%, 53.3% and 0.568, p = 0.404), and of MMP-9 were (53.9%, 40% and 0.660, p = 0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, p < 0.001), and that of CD34 + CD38 − CSCs were (78.9%, 73.3% and 0.855, p < 0.001). Increased TIMP-1 expression associated with the high-risk disease (p < 0.001). CD34 + CD38 − CSCs and MMP-2 overexpression associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (p < 0.05). TIMP-1 overexpression is associated with shorter DFS and OS rates (p = 0.009 and p = 0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, p = 0.046], and CD34 + CD38 − CSCs [OR: 6.873, p = 0.005] could be potential independent diagnostic factors for pediatric ALL. Conclusion: TIMP-1 and CD34 + CD38 − CSCs could be possible useful diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

show abstract

Section: Introductionmentioning

confidence: 79%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Role of matrix metalloproteinase MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP-1) in the clinical progression of pediatric acute lymphoblastic leukemia

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Many recent studies reported mutational and phenotypic changes that induce LSC-like properties, which were supported by BMM [11,12]. These phenotypic changes included upregulation of CD34, CD133, P-glycoprotein and BCRP/ABCG2, as well as downregulation of CD38 [11].…”

Section: Introductionmentioning

confidence: 79%

“…A Growing body of evidence suggests that leukemia stem cells (LSCs) is a subset of cancer cells that maintain chemo-resistance and relapse [9]. These CSCs were reported in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), but their role in ALL is still unclear [10,11].…”

Section: Introductionmentioning

confidence: 99%

Role of Matrix Metalloproteinase MMP-2, MMP-9 and Tissue Inhibitor of Metalloproteinase (TIMP-1) in Clinical Progression of Pediatric Acute Lymphoblastic Leukemia

Saleh

Khalil

Abdellateif

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Matrix metalloproteinases (MMPs) play a crucial role in cancer progression and metastasis, however their role in pediatric Acute lymphoblastic leukemia (ALL) is still unrevealed.Methods: The diagnostic, prognostic and predictive value of tissue inhibitor of metalloproteinase (TIMP-1), MMP-2, MMP-9 and CD34+CD38- CSCs were assessed in bone marrow (BM) samples of 76 ALL children using Flow Cytometry analysis. Results: There was a significant increase in TIMP-1 [1.52 (0.41-10) versus 0.91(0.6-1.12); respectively, P<0.001], and CSCs CD84+CD38- [1 (0.03-18.6) versus 0.3 (0.01-1.1), P<0.001] expression in ALL patients compared to controls. While there were no significant differences regarding MMP-2 and MMP-9 expression between the two groups. The sensitivity, specificity, AUC of MMP-2 were (80.3%, 53.3% and 0.568, P=0.404), and that of MMP-9 were (53.9%, 40% and 0.660, P=0.053). While that of TIMP-1 were (78.9%, 100% and 0.892, P<0.001), and that of CSCs CD34+ CD38- were (78.9%, 73.3% and 0.855, P<0.001). There was a significant association between MMP-2 overexpression and MRD at day-15, increased BM blast cell count at diagnosis and at day-15, (P=0.020, P=0.047 and P=0.001). Increased TIMP-1 expression associated with the high-risk disease (P<0.001), increased BM blast cell count at diagnosis and at day-15 (P=0.033 and P=0.001), as well as MRD at day 15 and day 42 (P<0.001 for both). CD34+CD38- CSCs associated with MRD at day-15, increased BM blast cell count at diagnosis and at day-15 (P=0.015, P=0.005 and P=0.003). TIMP-1 overexpression associated with shorter DFS and OS rates (P=0.009 and P=0.048). Multivariate logistic regression analysis showed that both TIMP-1 [OR: 4.224, P=0.046], and CD34+CD38- CSCs [OR: 6.873, P=0.005] are independent diagnostic factors for pediatric ALL.Conclusion: TIMP-1 and CD34+CD38- CSCs could be useful independent diagnostic markers for pediatric ALL. Also, TIMP-1 is a promising prognostic marker for poor outcome of the patients.

show abstract

High CD34 surface expression in BCP‐ALL predicts poor induction therapy response and is associated with altered expression of genes related to cell migration and adhesion

et al. 2022

View full text Add to dashboard Cite

show abstract

Close interaction with bone marrow mesenchymal stromal cells induces the development of cancer stem cell-like immunophenotype in B cell precursor acute lymphoblastic leukemia cells

Cited by 15 publications

References 32 publications

Role of matrix metalloproteinase MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP-1) in the clinical progression of pediatric acute lymphoblastic leukemia

Role of matrix metalloproteinase MMP-2, MMP-9 and tissue inhibitor of metalloproteinase (TIMP-1) in the clinical progression of pediatric acute lymphoblastic leukemia

Role of Matrix Metalloproteinase MMP-2, MMP-9 and Tissue Inhibitor of Metalloproteinase (TIMP-1) in Clinical Progression of Pediatric Acute Lymphoblastic Leukemia

High CD34 surface expression in BCP‐ALL predicts poor induction therapy response and is associated with altered expression of genes related to cell migration and adhesion

Contact Info

Product

Resources

About