Contributions
Abstract: PB1812
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a malignant myeloproliferative neoplasm, which is characterized by t(9;22)(q34.1;q11.21) translocation, also known as the Philadelphia chromosome (Ph). The resulting fusion gene BCR-ABL1 encodes a constitutively active tyrosine kinase that dictates the pathophysiology of CML. Tyrosine kinase inhibitors (TKIs) have been shown to efficiently inhibit not only the Bcr-Abl kinase, but also act on other cell surface tyrosine kinase receptors, such as the platelet-derived growth factor receptor (PDGF-R). Similar receptors are vital in neurotrophin-mediated signaling pathways, for example TrkB receptor for brain-derived neurotrophic factor (BDNF). PDGF is a potent mitogen for cells of mesenchymal origin and plays a significant role in angiogenesis, a process which has recently been recognized as crucial in growth and survival of neoplastic cells of the hematopoietic system. BDNF acts on certain neurons of the central nervous system and the peripheral nervous system and has a wide role in neuroprotection and neuroregeneration. However, the exact roles of PDGF, BDNF and their receptors in normal and malignant hematopoiesis remain unclear.
Aims
In this study we aimed to investigate the levels of PDGF-AA and BDNF in plasma from CML patients and, where possible, to identify how TKI treatment affects these proteins levels.
Methods
Peripheral blood samples were obtained from newly diagnosed CML patients (n=5), CML patients treated with TKIs (n=5) and healthy controls (n=10). Informed consent was obtained from all subjects included in the study. Plasma PDGF-AA and BDNF levels were analyzed using Luminex technology with Human Neurodegenerative disease Panel 3 kit (Merck Millipore, Billerica, USA).
Results
We have observed that PDGF-AA levels were elevated in CML group (both before and during TKI treatment) compared to controls. Interestingly, we have noticed that PDGF-AA level for newly diagnosed CML patients was higher compared to TKI-receivers (p < 0,05). In case of BDNF, we have observed subtle changes between the tested groups: BDNF level in newly diagnosed CML subjects was lower compared to controls (p < 0,05), but in TKI-receivers the level was comparable to control group (p > 0,05). We have also tested one patient in subsequent time points (at diagnosis, 3 months with TKIs, 6 months with TKIs) for both PDGF-AA and BDNF - we have observed PDGF levels drop and BDNF rise with time.
Conclusion
In our study we have demonstrated that PDGF-AA and BDNF are feasible targets for plasma proteomic analysis in CML patients, both for studying general patterns of protein expression and also for identifying proteins differentially expressed before and during TKI treatment. We have shown that PDGF level drops down after TKI treatment, while on the opposite BDNF level in plasma raises with time in CML patients receiving TKIs. We have also monitored these proteins levels over time in the same subject, but this requires a larger study group to draw meaningful conclusions. Further studies are required to elucidate the PDGF, BDNF and possibly other growth factors, neurotrophins and their receptors role in normal and malignant hematopoiesis.
Session topic: 7. Chronic myeloid leukemia - Biology
Keyword(s): Tyrosine kinase inhibitor, Protein Expression, Chronic myeloid leukemia, BCR-ABL
Abstract: PB1812
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a malignant myeloproliferative neoplasm, which is characterized by t(9;22)(q34.1;q11.21) translocation, also known as the Philadelphia chromosome (Ph). The resulting fusion gene BCR-ABL1 encodes a constitutively active tyrosine kinase that dictates the pathophysiology of CML. Tyrosine kinase inhibitors (TKIs) have been shown to efficiently inhibit not only the Bcr-Abl kinase, but also act on other cell surface tyrosine kinase receptors, such as the platelet-derived growth factor receptor (PDGF-R). Similar receptors are vital in neurotrophin-mediated signaling pathways, for example TrkB receptor for brain-derived neurotrophic factor (BDNF). PDGF is a potent mitogen for cells of mesenchymal origin and plays a significant role in angiogenesis, a process which has recently been recognized as crucial in growth and survival of neoplastic cells of the hematopoietic system. BDNF acts on certain neurons of the central nervous system and the peripheral nervous system and has a wide role in neuroprotection and neuroregeneration. However, the exact roles of PDGF, BDNF and their receptors in normal and malignant hematopoiesis remain unclear.
Aims
In this study we aimed to investigate the levels of PDGF-AA and BDNF in plasma from CML patients and, where possible, to identify how TKI treatment affects these proteins levels.
Methods
Peripheral blood samples were obtained from newly diagnosed CML patients (n=5), CML patients treated with TKIs (n=5) and healthy controls (n=10). Informed consent was obtained from all subjects included in the study. Plasma PDGF-AA and BDNF levels were analyzed using Luminex technology with Human Neurodegenerative disease Panel 3 kit (Merck Millipore, Billerica, USA).
Results
We have observed that PDGF-AA levels were elevated in CML group (both before and during TKI treatment) compared to controls. Interestingly, we have noticed that PDGF-AA level for newly diagnosed CML patients was higher compared to TKI-receivers (p < 0,05). In case of BDNF, we have observed subtle changes between the tested groups: BDNF level in newly diagnosed CML subjects was lower compared to controls (p < 0,05), but in TKI-receivers the level was comparable to control group (p > 0,05). We have also tested one patient in subsequent time points (at diagnosis, 3 months with TKIs, 6 months with TKIs) for both PDGF-AA and BDNF - we have observed PDGF levels drop and BDNF rise with time.
Conclusion
In our study we have demonstrated that PDGF-AA and BDNF are feasible targets for plasma proteomic analysis in CML patients, both for studying general patterns of protein expression and also for identifying proteins differentially expressed before and during TKI treatment. We have shown that PDGF level drops down after TKI treatment, while on the opposite BDNF level in plasma raises with time in CML patients receiving TKIs. We have also monitored these proteins levels over time in the same subject, but this requires a larger study group to draw meaningful conclusions. Further studies are required to elucidate the PDGF, BDNF and possibly other growth factors, neurotrophins and their receptors role in normal and malignant hematopoiesis.
Session topic: 7. Chronic myeloid leukemia - Biology
Keyword(s): Tyrosine kinase inhibitor, Protein Expression, Chronic myeloid leukemia, BCR-ABL