BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia

Heesch, Sandra; Schlee, Cornelia; Neumann, Martin; Stroux, Andrea; Kühnl, Andrea; Schwartz, Stefan; Haferlach, Torsten; Goekbuget, Nicola; Hoelzer, Dieter; Thiel, Eckhard; Hofmann, W; Cd, Baldus

doi:10.1038/leu.2010.130

Cited by 43 publications

(49 citation statements)

References 45 publications

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“…49 Conversely, IGFBP7 was found to induce senescence in T-ALL cell lines. 50 The later results were obtained using IGFBP7 at concentrations above 5 mg/ml. At these high IGFBP7 concentrations, we also found an inhibitory effect on the proliferation of B-lineage ALL cell lines (data not shown).…”

Section: Discussionmentioning

confidence: 96%

IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

et al. 2011

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The interaction of acute lymphoblastic leukemia (ALL) blasts with bone marrow (BM) stromal cells (BMSCs) has a positive impact on ALL resistance to chemotherapy. We investigated the modulation of a series of putative asparaginase-resistance/ sensitivity genes in B-precursor ALL cells upon coculture with BMSCs. Coculture with stromal cells resulted in increased insulinlike growth factor (IGF)-binding protein 7 (IGFBP7) expression by ALL cells. Assays with IGFBP7 knockdown ALL and stromal cell lines, or with addition of recombinant rIGFBP7 (rIGFBP7) to the culture medium, showed that IGFBP7 acts as a positive regulator of ALL and stromal cells growth, and significantly enhances in-vitro resistance of ALL to asparaginase. In these assays, IGFBP7 function occurred mainly in an insulin-and stromal-dependent manner. ALL cells were found to contribute substantially to extracellular IGFBP7 levels in the conditioned coculture medium. Diagnostic BM plasma from children with ALL had higher levels of IGFBP7 than controls. IGFBP7, in an insulin/IGF-dependent manner, enhanced asparagine synthetase expression and asparagine secretion by BMSCs, thus providing a stromal-dependent mechanism by which IGFBP7 protects ALL cells against asparaginase in this coculture system. Importantly, higher IGFBP7 mRNA levels were associated with lower leukemia-free survival (Cox regression model, P ¼ 0.003) in precursor B-cell Ph(À) ALL patients (n ¼ 147) treated with a contemporary polychemotherapy protocol.

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Section: Discussionmentioning

confidence: 96%

IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

et al. 2011

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“…IGFBP7 was strongly correlated with BAALC-expression, implicating IGFBP7 in acute leukemia [128]. A b e r r e n t e x p r e s s i o n o f I G F B P 7 i n a d u l t leukemia was correlated with chemotherapy resistance and inferior survival.…”

Section: Acute Leukemiamentioning

confidence: 86%

“…A b e r r e n t e x p r e s s i o n o f I G F B P 7 i n a d u l t leukemia was correlated with chemotherapy resistance and inferior survival. Addition of IGFBP7 to leukemic cell lines inhibited cell growth without induction of apoptosis or senescence, suggesting a role of IGFBP7 in contributing to drug resistance through reduced sensitivity to cytostatic drugs [128]. Aberrently increased levels of IGFBP7 were found in CSF from children with acute lymphoblastic leukemia, implicating IGFBP7 with a more aggressive subtype of ALL [129].…”

Section: Acute Leukemiamentioning

confidence: 96%

Insulin-Like-Growth Factor-Binding-Protein 7: An Antagonist to Breast Cancer

Benatar¹,

Amemiya²,

Yang³

et al. 2011

Breast Cancer - Focusing Tumor Microenvironment, Stem Cells and Metastasis

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“…In acute myeloid leukemia (AML), IGFBP7 was found to be coexpressed with the BAALC (brain and acute leukemia, cytoplasmic) gene. Furthermore, high IGFBP7 level was associated with stem cell features and treatment failure in T-ALL [16]. There are contradictory studies in the literature regarding the role of IGFBP7: In some studies, it has been reported as a tumor suppressor [17,18], while in others as an oncogene.…”

Section: Igfbp7 Expression In Esccmentioning

confidence: 97%

“…IGF-BP7 is a secreted protein. It has been reported as a novel marker for acute leukemia [16]. In acute myeloid leukemia (AML), IGFBP7 was found to be coexpressed with the BAALC (brain and acute leukemia, cytoplasmic) gene.…”

Section: Igfbp7 Expression In Esccmentioning

confidence: 99%

Evaluation of protein expression pattern of stanniocalcin 2, insulin-like growth factor-binding protein 7, inhibin beta A and four and a half LIM domains 1 in esophageal squamous cell carcinoma

Kashyap

Pawar

Keerthikumar

et al. 2013

CBM

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Abstract. The pathogenesis of esophageal squamous cell carcinoma (ESCC) involves both genetic and environmental factors. Previously, we have carried out gene and protein expression profiling of ESCC using DNA microarrays and mass spectrometrybased quantitative proteomics, respectively. These studies resulted in identification of several potential biomarkers of ESCC, some with known reports of differential expression in the scientific literature and others that were novel observations from our studies. We report systematic validation of selected markers from our studies on a larger cohort of cancer tissue sections by immunohistochemical labeling of tissue microarrays. We have validated expression of insulin-like growth factor-binding protein 7 (IGFBP7), stanniocalcin 2 (STC2), inhibin beta A (INHBA) and four and a half LIM domains 1 (FHL1). Immunohistochemical labeling with anti-stanniocalcin 2 antibody demonstrated its overexpression in 132/140 (94%) cases, IGFBP7 showed overexpression in 127/140 (91%) cases and overexpression of INHBA was observed in 62/105 (59%) of ESCC cases. In contrast, FHL1 expression was observed only in 12/143 (8%) of ESCC cases suggesting its possible involvement in tumor suppression. These data suggest that IGFBP7, INHBA, STC2 and FHL1 might play an important role in ESCC tumorigenesis, which can be explored in future studies. Overall, our findings open up new avenues for development of novel therapeutics and/or diagnostic approaches in ESCC.

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BAALC-associated gene expression profiles define IGFBP7 as a novel molecular marker in acute leukemia

Cited by 43 publications

References 45 publications

IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

IGFBP7 participates in the reciprocal interaction between acute lymphoblastic leukemia and BM stromal cells and in leukemia resistance to asparaginase

Insulin-Like-Growth Factor-Binding-Protein 7: An Antagonist to Breast Cancer

Evaluation of protein expression pattern of stanniocalcin 2, insulin-like growth factor-binding protein 7, inhibin beta A and four and a half LIM domains 1 in esophageal squamous cell carcinoma

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