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- Lagunas-Rangel, Francisco Alejandro
(författare)
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DNA damage accumulation and repair defects in FLT3‐ITD acute myeloid leukemia : Implications for clonal evolution and disease progression
- 2023
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Ingår i: Hematological Oncology. - : John Wiley & Sons. - 0278-0232 .- 1099-1069. ; 41:1, s. 26-38
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Forskningsöversikt (refereegranskat)abstract
- Acute myeloid leukemia is a group of hematological diseases that have a high mortality rate. During the development of this pathology, hematopoietic cells acquire chromosomal rearrangements and multiple genetic mutations, including FLT3-ITD. FLT3-ITD is a marker associated with a poor clinical prognosis and involves the activation of pathways such as PI3K/AKT, MAPK/ERK, and JAK/STAT that favor the survival and proliferation of leukemic cells. In addition, FLT3-ITD leads to overproduction of reactive oxygen species and defective DNA damage repair, both implicated in the appearance of new mutations and leukemic clones. Thus, the purpose of this review is to illustrate the molecular mechanisms through which FLT3-ITD generates genetic instability and how it facilitates clonal evolution with the generation of more resistant and aggressive cells. Likewise, this article discusses the feasibility of combined therapies with FLT3 inhibitors and inhibitors of DNA repair pathways.
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- Lindberg, Åsa, et al.
(författare)
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Pre-treatment health-related quality of life parameters have prognostic impact in patients >65 years with newly diagnosed mantle cell lymphoma : The Nordic Lymphoma Group MCL4 (LENA-BERIT) experience
- 2022
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Ingår i: Hematological Oncology. - : Wiley. - 0278-0232 .- 1099-1069. ; 40:1, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- Mantle cell lymphoma (MCL) is a rare, often aggressive type of B-cell lymphoma with poor survival and no cure. Cancer and cancer treatment has a negative impact on health-related quality of life (HRQOL) both during active disease and in the long term, and improvement of HRQOL is a crucial objective of cancer therapy in older patients and no curative intent. Baseline HRQOL has in other lymphoma populations been shown to be predictive of outcome. Here, we explored HRQOL, and its association with survival, by the EORTC QLQ-C30 questionnaire, before, during and after chemotherapy in a patient cohort with MCL, treated within the NLG-MCL4 trial, designed to evaluate the addition of lenalidomide (LEN) to rituximab-bendamustine (R-B) as first-line treatment. Fifty-one patients were enrolled, median age was 71 years (range 62–84), 37 were men (73%). Pre-treatment HRQOL was similar to scores from the reference population with healthy individuals. During treatment, HRQOL deteriorated, but reverted to the same level as the reference population after treatment. There was a correlation between physical function (p = 0.001) and role function (p = 0.006) at baseline and WHO performance status, but not with other clinical or genetic prognostic factors. None of the baseline factors were predictive for treatment related to HRQOL in this cohort. Pre-treatment physical (p = 0.011) and role function (p = 0.032) were independent factors associated with overall survival, and physical function (p = 0.002) was also associated with progression free survival. These findings may possibly be used to design support during treatment and improve rehabilitation. Further investigations are needed for assessment of long-term HRQOL.
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