Inflammation conjoins differentiation and resistance in AML
In this issue of Blood, Allen and colleagues provide insights into the mechanisms of resistance to MDM2 and BCL-2 inhibitors such as idasanutlin and venetoclax in acute myeloid leukemia (AML), particularly in monocytic subtypes (FAB M4/M5).1 The investigators describe a positive feedback loop of int...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
May 22 2025
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| In: |
Blood
Year: 2025, Volume: 145, Issue: 21, Pages: 2405-2407 |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood.2025028651 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1182/blood.2025028651
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| Author Notes: | Maike Janssen and Carsten Müller-Tidow |
| Summary: | In this issue of Blood, Allen and colleagues provide insights into the mechanisms of resistance to MDM2 and BCL-2 inhibitors such as idasanutlin and venetoclax in acute myeloid leukemia (AML), particularly in monocytic subtypes (FAB M4/M5).1 The investigators describe a positive feedback loop of interleukin-1 (IL-1)-tumor necrosis factor-α (TNF-α)-nuclear factor κB (NF-κB) pathway members regulated by CEBPB, which promotes monocytic differentiation and confers drug resistance.AML is a heterogeneous disease characterized by a block in myeloid differentiation leading to rapid expansion of leukemic blasts and bone marrow failure.2 The addition of the BCL-2 inhibitor venetoclax to hypomethylating agents (HMAs) leads to a significant improvement in response and survival compared with HMAs alone for older unfit adults with newly diagnosed AML resulting in the approval of venetoclax by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) in this setting. Despite the promising improvement in outcome, resistant disease and relapses remain frequent.3 Altered BCL-2 family member expression, especially of MCL-1, plays a key role in venetoclax resistance.4,5 The TP53 regulator MDM2 is expressed in the blasts of around 50% of patients with AML. Targeting MDM2 for the treatment of AML with small molecule inhibitors including idasanutlin6 is thus attractive, but responses are mixed. |
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| Item Description: | Gesehen am 12.09.2025 |
| Physical Description: | Online Resource |
| ISSN: | 1528-0020 |
| DOI: | 10.1182/blood.2025028651 |