Expression of BCL2 alternative proteins and association with outcome in CLL patients treated with venetoclax

Marques‐Piubelli, Mario L.; Schlette, Ellen; Khoury, Joseph D.; Furqan, Fateeha; Vega, Francisco; Soto, Luisa M. Solis; Wistuba, Ignacio I.; Wierda, William G.; Konopleva, Marina; Ferrajoli, Alessandra

doi:10.1080/10428194.2020.1861278

Cited by 7 publications

(4 citation statements)

References 37 publications

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“…Mild PTT inhibited the expression of PHF19, BCL-2A1, and TP53, and significantly promoted the expression of FOS, GADD45B, and TNFRSF10B, which eventually activated the apoptotic pathway. [30][31][32] It also activated heat shock proteins, such as HSPA1A, HSPA1B, and HSPA, which are associated with the MAPK signaling pathway. Although the activation of heat shock proteins can protect cells from heat damage, they can also activate the apoptotic pathway.…”

Section: Resultsmentioning

confidence: 99%

Nanoporous Gold Ring‐Integrated Photothermal Intraocular Lens for Active Prevention of Posterior Capsular Opacification

Liu

Chen

et al. 2022

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Posterior capsular opacification (PCO) is the leading complication after cataract surgery, and is mainly induced by the proliferation and migration of residual lens epithelial cells (LECs). Although numerous attempts have been made to reduce the incidence of PCO, this complication remains a critical challenge in postoperative visual recovery. This study aims to report a functionalized intraocular lens (R‐IOL) with a region‐confined photothermal effect for the active prevention of PCO after implantation. The outer rim of R‐IOL (non‐optical area) is decorated with a nanoporous gold (NPG) ring, which can effectively eliminate the LECs around R‐IOL, ultimately inhibiting the migration of LECs from the periphery to the visual axis center in the initial stage, and preventing the subsequent PCO. Furthermore, the mechanism of LECs elimination can be attributed to apoptosis induced by mild photothermal therapy. After in vivo implantation for 30 days, PCO is rarely observed in the R‐IOL group, whereas the considerably higher incidence of PCO (75%) is found in the pristine IOL (P‐IOL) group. The region‐confined photothermal effect based on NPG not only provides an active strategy to effectively prevent PCO, but also introduces new opportunities for the treatment of undesirable hyperplasia.

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Section: Resultsmentioning

confidence: 99%

Nanoporous Gold Ring‐Integrated Photothermal Intraocular Lens for Active Prevention of Posterior Capsular Opacification

Liu

Chen

et al. 2022

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“…[16][17][18] BH3 mimetics drugs are small molecules that mimic the function of the pro-apoptotic BH3-only proteins antagonizing the activity of antiapoptotic proteins. 13,17,18 The BCL2 inhibitor venetoclax has demonstrated to be effective in treating refractory hematological malignancies [13][14][15]19,20 ; still, the response as a single agent was limited in solid tumors. 14,15 Combined therapies with BCL2 plus MCL1 inhibitors are being studied.…”

Section: Discussionmentioning

confidence: 99%

Apoptosis Pathway–Associated Proteins Are Frequently Expressed in Melanoma: A Study of 32 Cases With Focus on Acral Lentiginous Melanoma

Ledesma,

Marques-Piubelli,

Li-Ning-Tapia

et al. 2024

The American Journal of Dermatopathology

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Acral lentiginous melanoma (ALM) is an aggressive type of cutaneous melanoma (CM) that arises on palms, soles, and nail units. ALM is rare in White population, but it is relatively more frequent in dark-skinned populations. There is an unmet need to develop new personalized and more effective treatments strategies for ALM. Increased expression of antiapoptotic proteins (ie, BCL2, MCL1) has been shown to contribute to tumorigenesis and therapeutic resistance in multiple tumor types and has been observed in a subset of ALM and mucosal melanoma cell lines in vivo and in vitro. However, little is known about their expression and clinical significance in patients with ALM. Thus, we assessed protein expression of BCL2, MCL1, BIM, and BRAF V600E by immunohistochemistry in 32 melanoma samples from White and Hispanic populations, including ALM and non-ALM (NALM). BCL2, MCL1, and BIM were expressed in both ALM and NALM tumors, and no significant differences in expression of any of these proteins were detected between the groups, in our relatively small cohort. There were no significant associations between protein expression and BRAF V600E status, overall survival, or ethnicity. In summary, ALM and NALM demonstrate frequent expressions of apoptosis-related proteins BCL2, MCL1, and BIM. Our findings suggest that patients with melanoma, including ALM, may be potential candidates for apoptosis-directed therapies.

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“…Indeed, BH3 profiling (see Section 3.1.3) has demonstrated that CLL cells in most patients are dependent on BCL-2 for survival [21]. Furthermore, CLL cells commonly express high levels of BH3-only pro-apoptotic proteins, such as BIM, causing cells to be primed for cell death but dependent on BCL-2 function [1,22].…”

Section: Apoptosis Dysregulation In Hematolymphoid Neoplasmsmentioning

confidence: 99%

Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions

Salah

DiNardo

Konopleva

et al. 2021

Cancers

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Intrinsic apoptotic pathway dysregulation plays an essential role in all cancers, particularly hematologic malignancies. This role has led to the development of multiple therapeutic agents targeting this pathway. Venetoclax is a selective BCL-2 inhibitor that has been approved for the treatment of chronic lymphoid leukemia and acute myeloid leukemia. Given the reported resistance to venetoclax, understanding the mechanisms of resistance and the potential biomarkers of response is crucial to ensure optimal drug usage and improved patient outcomes. Mechanisms of resistance to venetoclax include alterations involving the BH3-binding groove, BCL2 gene mutations affecting venetoclax binding, and activation of alternative anti-apoptotic pathways. Moreover, various potential genetic biomarkers of venetoclax resistance have been proposed, including chromosome 17p deletion, trisomy 12, and TP53 loss or mutation. This manuscript provides an overview of biomarkers that could predict treatment response to venetoclax.

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Expression of BCL2 alternative proteins and association with outcome in CLL patients treated with venetoclax

Cited by 7 publications

References 37 publications

Nanoporous Gold Ring‐Integrated Photothermal Intraocular Lens for Active Prevention of Posterior Capsular Opacification

Nanoporous Gold Ring‐Integrated Photothermal Intraocular Lens for Active Prevention of Posterior Capsular Opacification

Apoptosis Pathway–Associated Proteins Are Frequently Expressed in Melanoma: A Study of 32 Cases With Focus on Acral Lentiginous Melanoma

Potential Biomarkers for Treatment Response to the BCL-2 Inhibitor Venetoclax: State of the Art and Future Directions

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