Identification of Annexin A1 interacting proteins in chronic myeloid leukemia KCL22 cells

Colavita, Irene; Esposito, Nicola; Quintarelli, Concetta; Nigro, Ersilia; Pane, Fabrizio; Ruoppolo, Margherita; Salvatore, Francesco

doi:10.1002/pmic.201200444

Cited by 8 publications

(7 citation statements)

References 24 publications

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“…In addition, some reports have suggested that JAK activation is dependent on BCR-ABL, whereas others did not (Carlesso et al, 1996;Colavita et al, 2013;Hoelbl et al, 2010;Nair et al, 2012b;Coppo et al, 2006). Furthermore, it was reported that JAK inhibitors were only effective against CML when BCR-ABL was inhibited by nilotinib (Coppo et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…For example, we hypothesize that the survival of LSCs might not be affected by the inhibition of BCR-ABL kinase activity during IMA treatment. Therefore, it might be necessary to inhibit other signaling pathways in addition to BCR-ABL kinase activity (Corbin et al, 2011;Colavita et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, inhibition of the JAK/STAT pathway might represent a good target during the development of drugs for CML. It has been reported that JAK2 inhibitors, such as ruxolitinib (RUX), are effective against CML (Colavita et al, 2013;Quintarelli et al, 2014), and JAK inhibitors reinforced cell death within the bone marrow microenvironment in a mouse model (Nair et al, 2012a;Traer et al, 2012). Thus, the simultaneous inhibition of BCR-ABL and JAK2 might be a useful therapeutic strategy for overcoming tyrosine kinase inhibitor (TKI) resistance (Quintarelli et al, 2014;Traer et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Pharmacological inhibition of JAK3 enhances the antitumor activity of imatinib in human chronic myeloid leukemia

Yagi

Shimada

Sendo

2018

European Journal of Pharmacology

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Imatinib (IMA) is the standard treatment for CML; however, stopping IMA sometimes results in disease relapse, which suggests that leukemic stem cells (LSCs) remain in such patients, even after complete molecular remission has been achieved. Therefore, new strategies will be required to eradicate LSCs. The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway is part of the BCR-ABL signaling network, and it is activated in CML, especially in LSCs. JAK2 is known to be associated with CML survival, but the role of JAK3 in CML remains unknown. The antitumor effects of IMA and a JAK3 inhibitor, tofacitinib were examined using the MTT assay in K562 and KCL22. To investigate the mechanisms of action of IMA and the JAK inhibitors in CML cells, we examined apoptosis, the cell cycle, and JAK-STAT signaling using flow cytometry, immunofluorescent microscopy, and Western blotting. The pharmacological inhibition of JAK3 by tofacitinib synergistically enhanced the antitumor effects of IMA in CML cells. Furthermore, the administration of IMA plus a JAK inhibitor reduced the expression of stem cells markers, such as ABCG2 and ALDH1A1. Co-blocking JAK3 with IMA and a JAK3 inhibitor might represent a new treatment strategy for eradicating LSCs and preventing CML relapses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Pharmacological inhibition of JAK3 enhances the antitumor activity of imatinib in human chronic myeloid leukemia

Yagi

Shimada

Sendo

2018

European Journal of Pharmacology

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“…Unfortunately,t he BCR-ABL1-independent mechanisms of resistance in CML have been poorly characterized. [28][29][30][31] Finally the activity of ac ompound against ac ell line does not depend only on the isolated activity against an enzymet arget but also depends on cellular permeation, cellular compartment localization,s tability of the compound in cells and promiscuity of compound toward binding to other cellular proteins (both kinase and non-kinase targets). Ac ompound that potently inhibits ABL1 but also binds to other cellular macromolecules and/or localizes into compartments that BCR-ABL1 does not reside will not display the same potencya gainst the target protein as was seen in an in vitro assay.C ompounds 16 (HSN608)a nd 15 (HSN459)a re of interestb ecause in addition to potent activity againstd rug-resistant CML cell line, KCL22-IR, they have lower logP values (2.3 and 2.7, respectively)t han the rest of the active compounds and therefore are more drug-like in comparison.…”

Section: Aminoisoquinolinesand Aminonaphthyridines Potently Inhibit Tmentioning

confidence: 99%

Alkynylnicotinamide‐Based Compounds as ABL1 Inhibitors with Potent Activities against Drug‐Resistant CML Harboring ABL1(T315I) Mutant Kinase

et al. 2018

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The introduction of imatinib into the clinical scene revolutionized the treatment of chronic myelogenous leukemia (CML). The overall eight-year survival rate for CML has increased from about 6 % in the 1970s to over 90 % in the imatinib era. However, about 20 % of CML patients harbor primary or acquired resistance to tyrosine kinase inhibitors. ABL1 point mutations in the BCR-ABL1 fusion protein, such as ABL1(T315I), typically emerge after prolonged kinase inhibitor treatment. Ponatinib (AP24534) is currently the only approved CML drug that is active against the ABL1(T315I) mutation. However, ponatinib has severe cardiovascular toxicities; hence, there have been efforts to find safer CML drugs that work against ABL1 secondary mutations. We reveal that isoquinoline- or naphthyridine-based compounds, such as HSN431, HSN576, HSN459, and HSN608 potently inhibit the enzymatic activities of ABL1, ABL1(T315I), and ABL1(E255K). These compounds inhibit the proliferation of ABL1-driven CML cell lines, K652 and KCL22 as well as the drug-resistant cell line, KCL22-IR, which harbors the secondary mutated ABL1(T315I) kinase.

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“…However, resistance to TKI is a vital aspect of Ph + ALL due to the emergence of breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL) mutations (2–5). Previous studies have suggested that upon TKI treatment pressure, chronic myelogenous leukemia (CML) stem cells survive due to BCR-ABL kinase-independent mechanisms (6–9). …”

Section: Introductionmentioning

confidence: 99%

Growth of tyrosine kinase inhibitor-resistant Philadelphia-positive acute lymphoblastic leukemia: Role of bone marrow stromal cells

Zhang

Yang

et al. 2017

Oncology Letters

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Human bone marrow stromal cells (hBMSCs) may contribute to the growth of tyrosine kinase inhibitor (TKI)-resistant chronic myelogenous leukemia (CML). However, there are certain differences in biology between CML and Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Little is known about the role and mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study co-cultured hBMSCs with the TKI-resistant SUP-B15. Next, the proliferation of SUP-B15 was detected using a Cell Counting Kit-8. Additionally, quantitative polymerase chain reaction and flow cytometry were used to detect the expression of the associated genes and proteins. The present study explores the role and mechanism of hBMSCs on the growth of TKI-resistant Ph+ ALL. The current study showed that hBMSCs promoted the proliferation of TKI-resistant Ph+ ALL. This was shown by the increase in cells in the S+G2-M phase of the cell cycle. It was also found that the expression of cyclins A, C, D1 and E was increased. Apoptosis was inhibited through upregulation of anti-apoptotic genes [B-cell lymphoma-2 (BCL-2) and BCL-extra large] and downregulation of apoptotic genes (BCL-XS, BCL-2-associated X protein, and caspases 3, 7 and 9). Expression of the breakpoint cluster region (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL) gene, Wnt5a, and Wnt signaling pathway-associated genes (glycogen synthase kinase-3β, β-catenin, E-cadherin and phosphoinositide 3-kinase) and transcription factors (c-myc, ephrin type-B2, fibroblast growth factor 20 and matrix metalloproteinase 7) was also increased. Furthermore, the expression of drug resistance genes (low-density lipoprotein receptor, multidrug resistance-associated protein and multi-drug resistance gene) was increased and the expression of anti-oncogenes (death-associated protein kinase and interferon regulatory factor-1) was decreased. It was concluded that hBMSCs promote the growth of TKI-resistant Ph+ ALL by these aforementioned mechanisms. Therefore, targeting hBMSCs may be a promising approach for preventing the growth of TKI-resistant Ph+ ALL.

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Identification of Annexin A1 interacting proteins in chronic myeloid leukemia KCL22 cells

Cited by 8 publications

References 24 publications

Pharmacological inhibition of JAK3 enhances the antitumor activity of imatinib in human chronic myeloid leukemia

Pharmacological inhibition of JAK3 enhances the antitumor activity of imatinib in human chronic myeloid leukemia

Alkynylnicotinamide‐Based Compounds as ABL1 Inhibitors with Potent Activities against Drug‐Resistant CML Harboring ABL1(T315I) Mutant Kinase

Growth of tyrosine kinase inhibitor-resistant Philadelphia-positive acute lymphoblastic leukemia: Role of bone marrow stromal cells

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