THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIA
In spite recent progresses, acute myeloid leukemia (AML) remains a disease associated with poor prognosis, particularly in older AML patients unfit to tolerate intensive chemotherapy treatment. The development and introduction in therapy of the drug Venetoclax, a potent BH3 mimetic targeting the an...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
PAGEPress Publications
2022-10-01
|
| Series: | Mediterranean Journal of Hematology and Infectious Diseases |
| Online Access: | https://www.mjhid.org/index.php/mjhid/article/view/5150 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846144273779523584 |
|---|---|
| author | Elvira Pelosi Germana Castelli Ugo Testa |
| author_facet | Elvira Pelosi Germana Castelli Ugo Testa |
| author_sort | Elvira Pelosi |
| collection | DOAJ |
| description |
In spite recent progresses, acute myeloid leukemia (AML) remains a disease associated with poor prognosis, particularly in older AML patients unfit to tolerate intensive chemotherapy treatment. The development and introduction in therapy of the drug Venetoclax, a potent BH3 mimetic targeting the antiaopoptotic protein BCL-2, inducing apoptosis of leukemic cells, has shown to be a promising treatment for newly diagnosed, relapsed and refractory AML patients ineligible for induction chemotherapy. Combination treatments using Ventoclax and a hypomethylating agent (azacytidine or decitabine) or low-intensity chemotherapy have shown in newly diagnosed patients variable response rates, with highly responsive patients with NPM1, IDH1-IDH2, TET2 and RUNX1 mutations and with scarcely responsive patients with FLT3, TP53 and ASXL1 mutations, complex karyotypes and secondary AMLs. Patients with refractory/relapsing disease are less responsive to Venetoclax-based regimens.
However, in the majority of patients the responses have only a limited duration and development of resistance is frequently observed. Understanding mechanisms of resistance is of crucial importance for the development of new strategies and identification of rational drug combination regimens. In this context, two strategies seem to be promising: (i) triplet therapies based on the combined administration of Venetoclax, a hypomethylating agent (or low-dose chemotherapy) and an agent targeting a specific genetic alteration of leukemic cells (i.e., FLT3 inhibitors in FLT3-mutated AMLs) or an altered signaling pathway; (ii) combination therapies based on the administration of two BH3 mimetics (i.e., BCL-2 +MCL-1 mimetics) and a hypomethylating agent.
|
| format | Article |
| id | doaj-art-2a47a1ca9b0a4339a7942a36a35c8b11 |
| institution | Kabale University |
| issn | 2035-3006 |
| language | English |
| publishDate | 2022-10-01 |
| publisher | PAGEPress Publications |
| record_format | Article |
| series | Mediterranean Journal of Hematology and Infectious Diseases |
| spelling | doaj-art-2a47a1ca9b0a4339a7942a36a35c8b112024-12-02T07:57:25ZengPAGEPress PublicationsMediterranean Journal of Hematology and Infectious Diseases2035-30062022-10-01141THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIAElvira PelosiGermana CastelliUgo Testa0ISS In spite recent progresses, acute myeloid leukemia (AML) remains a disease associated with poor prognosis, particularly in older AML patients unfit to tolerate intensive chemotherapy treatment. The development and introduction in therapy of the drug Venetoclax, a potent BH3 mimetic targeting the antiaopoptotic protein BCL-2, inducing apoptosis of leukemic cells, has shown to be a promising treatment for newly diagnosed, relapsed and refractory AML patients ineligible for induction chemotherapy. Combination treatments using Ventoclax and a hypomethylating agent (azacytidine or decitabine) or low-intensity chemotherapy have shown in newly diagnosed patients variable response rates, with highly responsive patients with NPM1, IDH1-IDH2, TET2 and RUNX1 mutations and with scarcely responsive patients with FLT3, TP53 and ASXL1 mutations, complex karyotypes and secondary AMLs. Patients with refractory/relapsing disease are less responsive to Venetoclax-based regimens. However, in the majority of patients the responses have only a limited duration and development of resistance is frequently observed. Understanding mechanisms of resistance is of crucial importance for the development of new strategies and identification of rational drug combination regimens. In this context, two strategies seem to be promising: (i) triplet therapies based on the combined administration of Venetoclax, a hypomethylating agent (or low-dose chemotherapy) and an agent targeting a specific genetic alteration of leukemic cells (i.e., FLT3 inhibitors in FLT3-mutated AMLs) or an altered signaling pathway; (ii) combination therapies based on the administration of two BH3 mimetics (i.e., BCL-2 +MCL-1 mimetics) and a hypomethylating agent. https://www.mjhid.org/index.php/mjhid/article/view/5150 |
| spellingShingle | Elvira Pelosi Germana Castelli Ugo Testa THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIA Mediterranean Journal of Hematology and Infectious Diseases |
| title | THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIA |
| title_full | THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIA |
| title_fullStr | THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIA |
| title_full_unstemmed | THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIA |
| title_short | THE GROWING ROLE OF THE BH3 MIMETIC DRUG VENETOCLAX IN THE THERAPY OF ACUTE MYELOID LEUKEMIA |
| title_sort | growing role of the bh3 mimetic drug venetoclax in the therapy of acute myeloid leukemia |
| url | https://www.mjhid.org/index.php/mjhid/article/view/5150 |
| work_keys_str_mv | AT elvirapelosi thegrowingroleofthebh3mimeticdrugvenetoclaxinthetherapyofacutemyeloidleukemia AT germanacastelli thegrowingroleofthebh3mimeticdrugvenetoclaxinthetherapyofacutemyeloidleukemia AT ugotesta thegrowingroleofthebh3mimeticdrugvenetoclaxinthetherapyofacutemyeloidleukemia AT elvirapelosi growingroleofthebh3mimeticdrugvenetoclaxinthetherapyofacutemyeloidleukemia AT germanacastelli growingroleofthebh3mimeticdrugvenetoclaxinthetherapyofacutemyeloidleukemia AT ugotesta growingroleofthebh3mimeticdrugvenetoclaxinthetherapyofacutemyeloidleukemia |