Mutations in chronic myelomonocytic leukemia and their prognostic relevance

Jian, Jinli; Qiao, Yi; Li, Y.; Guo, Yuancheng; Ma, Haiying; Liu, Bei

doi:10.1007/s12094-021-02585-x

Cited by 10 publications

(12 citation statements)

References 92 publications

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“…In fact, CPSS-Mol may be a superior method for calculating risk and deciding on treatment, as patients classified as low-risk by CPSS may well benefit from the treatment that would be indicated by CPSS-Mol. In line with previous reports, the EZH2/ASXL1 co-mutation [ 22 , 46 , 47 ], present in three of our patients, and RUNX1 mutations [ 10 ], detected in 20.8% of our patients, were also associated with shorter OS ( p = 0.001 and p = 0.02, respectively). Interestingly, patients harboring a mutation in at least one of the transcription factors ( RUNX1 , GATA2 , SETBP1 , and CEBPA ) had shorter OS ( p = 0.001); to the best of our knowledge, this phenomenon has not been explored in previous studies.…”

Section: Discussionsupporting

confidence: 93%

“…The percentage of patients who progressed to AML in our study was also along the lines of previous reports [ 11 , 22 , 47 , 49 ]. The risk of AML transformation depends on the transformative aggressiveness of CMML and on the competing risk of dying before transformation, usually from comorbidities or consequences of cytopenia [ 37 ].…”

Section: Discussionsupporting

confidence: 91%

“…However, the DACOTA trial [ 52 ] proved that randomized clinical trials are feasible in CMML, and clinical trials in CMML are now ongoing. Enrollment in CMML-specific clinical trials or in exploratory trials of specific tumor biomarkers should be encouraged as the best way to clarify the molecular mechanisms behind CMML and to explore the efficacy of new drugs in this disease [ 22 , 24 , 47 , 65 , 66 ]. Nevertheless, until such time where we have reliable data from clinical trials, studies such as ours, based on real-world data, can provide valuable insight into the CMML mutational landscape and treatment outcomes.…”

Section: Discussionmentioning

confidence: 99%

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Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

Castaño-Díez

López‐Guerra

Bosch-Castañeda

et al. 2022

Cancers

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Despite emerging molecular information on chronic myelomonocytic leukemia (CMML), patient outcome remains unsatisfactory and little is known about the transformation to acute myeloid leukemia (AML). In a single-center cohort of 219 CMML patients, we explored the potential correlation between clinical features, gene mutations, and treatment regimens with overall survival (OS) and clonal evolution into AML. The most commonly detected mutations were TET2, SRSF2, ASXL1, and RUNX1. Median OS was 34 months and varied according to age, cytogenetic risk, FAB, CPSS and CPSS-Mol categories, and number of gene mutations. Hypomethylating agents were administered to 37 patients, 18 of whom responded. Allogeneic stem cell transplantation (alloSCT) was performed in 22 patients. Two-year OS after alloSCT was 60.6%. Six patients received targeted therapy with IDH or FLT3 inhibitors, three of whom attained a long-lasting response. AML transformation occurred in 53 patients and the analysis of paired samples showed changes in gene mutation status. Our real-world data emphasize that the outcome of CMML patients is still unsatisfactory and alloSCT remains the only potentially curative treatment. However, targeted therapies show promise in patients with specific gene mutations. Complete molecular characterization can help to improve risk stratification, understand transformation, and personalize therapy.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

Castaño-Díez

López‐Guerra

Bosch-Castañeda

et al. 2022

Cancers

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“…Hematological malignancies include lymphoma, myeloma, myeloproliferative neoplasms, myelodysplastic syndromes, and leukemia with several subtypes [ 1 ]. Leukemia is divided into lymphocytic and myeloid, which these two mentioned groups include acute and chronic groups.…”

Section: Introductionmentioning

confidence: 99%

The Hippo signaling pathway in leukemia: function, interaction, and carcinogenesis

Noorbakhsh¹,

Hayatmoghadam

Jamali

et al. 2021

Cancer Cell Int

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Cancer can be considered as a communication disease between and within cells; nevertheless, there is no effective therapy for the condition, and this disease is typically identified at its late stage. Chemotherapy, radiation, and molecular-targeted treatment are typically ineffective against cancer cells. A better grasp of the processes of carcinogenesis, aggressiveness, metastasis, treatment resistance, detection of the illness at an earlier stage, and obtaining a better therapeutic response will be made possible. Researchers have discovered that cancerous mutations mainly affect signaling pathways. The Hippo pathway, as one of the main signaling pathways of a cell, has a unique ability to cause cancer. In order to treat cancer, a complete understanding of the Hippo signaling system will be required. On the other hand, interaction with other pathways like Wnt, TGF-β, AMPK, Notch, JNK, mTOR, and Ras/MAP kinase pathways can contribute to carcinogenesis. Phosphorylation of oncogene YAP and TAZ could lead to leukemogenesis, which this process could be regulated via other signaling pathways. This review article aimed to shed light on how the Hippo pathway interacts with other cellular signaling networks and its functions in leukemia.

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“…16 The combination of TET2, SRSF2, and ASXL1 mutation is highly specific (98%) for the diagnosis of CMML and has prognostic implications. 17 Moreover, while IDH1 has been reported to have poor outcome in MDS. 18 Sequencing data establish a clonal relationship between both processes and confirm the specific neoplastic nature of the cutaneous infiltration.…”

Section: Discussionmentioning

confidence: 99%

Plasmacytoid Dendritic Cell Dermatosis Associated to Myeloproliferative/Myelodysplastic Neoplasms

Machan

Alonso-Domínguez²,

García³

et al. 2022

American Journal of Surgical Pathology

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Cutaneous lesions in the setting of myeloproliferative neoplasms and myelodysplastic syndromes are poorly understood. We report 6 patients with pruritic papular eruptions composed of mature T-lymphocytes with large clusters of CD123-positive cells. Double immunohistochemical studies demonstrated a lack of myeloid cell nuclear differentiation antigen in the CD123-positive cells, which expressed SPIB, confirming that they were mature plasmacytoid dendritic cells. Four patients were diagnosed with chronic myelomonocytic leukemia and 2 with myelodysplastic syndromes (AREB-I and myelodysplastic syndromes with 5q deletion, respectively). All patients had a long history of hematological alterations, mainly thrombocytopenia, preceding the cutaneous disorder. Nevertheless, the skin lesions developed in all cases coincidentally with either progression or full-establishment of their hematological disease. Most cutaneous lesions disappeared spontaneously or after corticosteroid treatment. Molecular studies performed in both bone marrow and cutaneous lesions in 2 patients demonstrated the same mutational profile, confirming the specific, neoplastic nature of these mature plasmacytoid dendritic cells-composed cutaneous lesions.

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Mutations in chronic myelomonocytic leukemia and their prognostic relevance

Cited by 10 publications

References 92 publications

Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

The Hippo signaling pathway in leukemia: function, interaction, and carcinogenesis

Plasmacytoid Dendritic Cell Dermatosis Associated to Myeloproliferative/Myelodysplastic Neoplasms

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