Current Therapy of the Patients with MDS: Walking towards Personalized Therapy

Palacios-Berraquero, María Luisa; Piérola, Ana Alfonso

doi:10.3390/jcm10102107

Cited by 11 publications

(20 citation statements)

References 85 publications

(101 reference statements)

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“…The introduction of hypomethylating drugs (HMAs) influenced the prognosis of MDS patients [23]. They remain the mainstay of therapy in newly diagnosed HR-MDS patients ineligible for allo-HSCT [2,24]. They are effective and less toxic, compared to intensive chemotherapy.…”

Section: Hypomethylating Drugsmentioning

confidence: 99%

“…Bcl-2 is an anti-apoptotic protein that is overexpressed in many cancers, also in MDS [24,60]. Venetoclax -an oral inhibitor targeting Bcl-2, known as an effective drug in the treatment of AML, has been used as the drug of HR-MDS, de novo MDS and MDS patients which are ineligible for intensive chemotherapy.…”

Section: Venetoclaxmentioning

confidence: 99%

“…It is well known that patients with TP53 mutated MDS/AML have a poor prognosis. Epranetapopt (APR-246) -a methylated derivative of PRIMA-1 stabilizes chemically mutant p53 protein [24]. Eprenetapopt is converted to methylene quinuclidinone (MQ), which binds changed p53 resulting in confirmation change and apoptosis [75].…”

Section: Eprenetapoptmentioning

confidence: 99%

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Therapeutic options in high-risk myelodysplastic syndrome

Maksymowicz

Moqbil

Machowiec

et al. 2023

Hematology in Clinical Practice

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Myelodysplastic syndromes (MDS) constitute a heterogeneous group of diseases characterised by ineffective haematopoiesis, dysplasia and cytopenias. The treatment for high-risk MDS (HR-MDS) depends on individual factors such as the stage of the disease, age, comorbidities, and infections.Allogeneic haematopoietic stem cell transplantation (allo-HSCT) with reduced intensity conditioning has allowed more HR-MDS patients to be transplant-eligible, regardless of age. Hypomethylating agents, including azacitidine and decitabine, remain the standard of care for HR-MDS patients who are not qualified for curative allo-HSCT. Combination therapy of azacitidine with some new drugs resulted in higher response rates than azacitidine in monotherapy. Other targeted therapies are under investigation. They include HMA with different antibodies targeting immune checkpoints -programmed cell death (ligand) 1, cytotoxic T lymphocyte antigen 4, T-cell immunoglobulin mucin-3 or cluster of differentiation 47. Larger studies are necessary to confirm their efficacy in the treatment of HR-MDS.

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Section: Hypomethylating Drugsmentioning

confidence: 99%

Section: Venetoclaxmentioning

confidence: 99%

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Therapeutic options in high-risk myelodysplastic syndrome

Maksymowicz

Moqbil

Machowiec

et al. 2023

Hematology in Clinical Practice

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“…To date, the only currently approved treatments for higher-risk MDS are allogeneic stem cell transplantation and hypomethylating agents, alone or in combination with novel drugs [ 5 ]. Azacitidine (AZA) is indeed a standard first-line therapy in high-risk MDS.…”

Section: Introductionmentioning

confidence: 99%

A miRNA screening identifies miR-192-5p as associated with response to azacitidine and lenalidomide therapy in myelodysplastic syndromes

et al. 2023

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Background miRNAs are small non-coding RNAs that regulate gene expression and are linked to cancer development and progression. miRNA profiles are currently studied as new prognostic factors or therapeutic perspectives. Among hematological cancers, myelodysplastic syndromes at higher risk of evolution into acute myeloid leukemia are treated with hypomethylating agents, like azacitidine, alone or in combination with other drugs, such as lenalidomide. Recent data showed that, during azacitidine and lenalidomide therapy, the concurrent acquisition of specific point mutations affecting inositide signalling pathways is associated with lack or loss of response to therapy. As these molecules are implicated in epigenetic processes, possibly involving miRNA regulation, and in leukemic progression, through the regulation of proliferation, differentiation and apoptosis, here we performed a new miRNA expression analysis of 26 high-risk patients with myelodysplastic syndromes treated with azacitidine and lenalidomide at baseline and during therapy. miRNA array data were processed, and bioinformatic results were correlated with clinical outcome to investigate the translational relevance of selected miRNAs, while the relationship between selected miRNAs and specific molecules was experimentally tested and proven. Results Patients’ overall response rate was 76.9% (20/26 cases): complete remission (5/26, 19.2%), partial remission (1/26, 3.8%), marrow complete remission (2/26, 7.7%), hematologic improvement (6/26, 23.1%), hematologic improvement with marrow complete remission (6/26, 23.1%), whereas 6/26 patients (23.1%) had a stable disease. miRNA paired analysis showed a statistically significant up-regulation of miR-192-5p after 4 cycles of therapy (vs baseline), that was confirmed by real-time PCR analyses, along with an involvement of BCL2, that was proven to be a miR-192-5p target in hematopoietic cells by luciferase assays. Furthermore, Kaplan–Meier analyses showed a significant correlation between high levels of miR-192-5p after 4 cycles of therapy and overall survival or leukemia-free survival, that was stronger in responders, as compared with patients early losing response and non-responders. Conclusions This study shows that high levels of miR-192-5p are associated with higher overall survival and leukemia-free survival in myelodysplastic syndromes responding to azacitidine and lenalidomide. Moreover, miR-192-5p specifically targets and inhibits BCL2, possibly regulating proliferation and apoptosis and leading to the identification of new therapeutic targets.

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“…The progressive addition of patient general condition evaluation to the stratification and management of MDS patients, coupled to the progressive use of NGS and targeted therapy, is paving the way to the much desired “personalized precision medicine” [ 6 , 7 ], in MDS patients. Palacios-Berrquero and Alfonso-Piérola (Department of Hematology, Clínica Universidad de Navarra, Pamplona, Spain) have summarized current MDS therapy in this Special Issue [ 8 ].…”

mentioning

confidence: 99%