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Small-Molecule Targeted Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Many cases are now known in which specific kinases are mutated in cancer cells. For example, a mutation of the protein kinase Abl (i.e., the cytoplasmic tyrosine kinase Bcr-Abl, which is constitutively active) is the main cause of Chronic Myeloid Leukemia (CML); it is present in virtually all cases of CML and is used as a diagnostic feature for this disease. It is also present in 15–30% of cases of adult acute lymphoblastic leukemia (ALL). This mutation was used as the basis for the design of inhibitors such as imatinib (Gleevec™). Other examples include mutations of the EGFR and B-RAF kinases which allowed the development of gefitinib (IressaTM) for lung cancer and vemurafenib (ZelborafTM) for melanoma, respectively.
Monoclonal Antibodies and Complement for Autologous Marrow Purging
Published in Adrian P. Gee, BONE MARROW PROCESSING and PURGING, 2020
An alternative to the method of C′ -mediated lysis outlined above has been described by Howell et al. (Figure 2).26 This method uses an automated cell processor, in particular the Haemonetics V50, to allow a constant infusion of C′ to be exposed to the tumor cells while centrifuging in the cell processor bowl. This has the advantage of allowing fresh complement to be continuously infused, while spent complement is removed, and in model systems, was capable of increasing tumor cell killing to 6 logs, a 2 log improvement over conventional treatment techniques. This permitted a single treatment to be used thereby saving both time and reagents. The use of a closed system also reduces the risk of contamination of the marrow during processing. The technique has been applied thus far to purging of myeloid leukemia cells in AML, but could have more general applications.
Testicular Cancer
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Nkwam Nkwam, Chitranjan J. Shukla, David A. Manson-Bahr, Taimur T. Shah, Farooq Khan
Cisplatin can cause a range of side effects. It is nephrotoxic and is contraindicated in patients with an eGFR of <60 mL/min/1.73 m2. Ototoxicity is another common side effect where patients present with tinnitus and hearing loss. An increased risk of acute myeloid leukaemia has also been observed along with increased risk of hypogonadism and cardiovascular disease.
Establishment and validation of prognostic nomogram in acute leukemia with trisomy 8
Published in Hematology, 2023
Tianxia Deng, Sheng Wang, Zhuonan Ran, Qiulian Liu, Mingxia Wang
The present study showed that the proportion of patents aged >51 years was significantly higher in the poor prognosis group than in the good prognosis group. Studies have shown that 60%∼85% of adults under 60 years of age can achieve complete remission after effective treatment, but in older patients over 60 years of age, the complete remission rate is only 40%∼60% [16]. The 5-year overall survival rate for young and middle-aged acute myeloid leukemia patients is <50%, compared with only about 10% for acute myeloid leukemia patients over 60 years of age [17]. This study showed that the proportion of incomplete disease remission after the first induction, the proportion of white blood cell count ≤ 20 × 109/L, and the proportion of chemotherapy alone were significantly higher in the poor prognosis group than in the good prognosis group. Chemotherapy is a common clinical treatment modality for acute leukemia, but even when patients achieve CR of their disease, the disease-free survival rate is only 40%∼50%. Clinicians believe that this outcome is associated with the development of chemotherapy resistance in patients [18]. In addition, chemotherapy may lead to acute complications in patients with acute myeloid leukemia. Allogeneic stem cell transplantation is an appropriate approach to reduce the leukemia relapse risk compared to standard chemotherapy, though it increases the risk of serious complications [19]. It has also been shown that white blood cell count is an important predictor of prognosis in patients with acute myeloid leukemia [20].
Analysis of Mean Corpuscular Volume and Red Cell Distribution Width in Patients with Aplastic Anemia
Published in Hemoglobin, 2023
Lingling Liu, Qiuhao Fu, Danfeng Zhang, Dandan Chen, Fang Wang, Rong Guo, Xinsheng Xie, Zhongxing Jiang, Jifeng Yu, Yingmei Li
A study on age-related clonal hematopoiesis associated with adverse outcomes examined whole-exome sequencing data from DNA in the peripheral blood cells of 17,182 unselected individuals with hematological phenotypes. The results suggest that elevated RDW levels were significantly associated with clonal hematopoiesis [35]. Abelson and his colleagues [36] investigated acute myeloid leukemia risk factors in healthy individuals. It demonstrated a significant correlation between RDW and acute myeloid leukemia progression risk. It is well-known that AA patients have clonal hematopoiesis, and approximately 10–20% of AA patients progress to MDS or acute myeloid leukemia [37–39]. We must continue to monitor these AA patients to investigate the effect of RDW on AA clone hematopoiesis and clonal evolution.
Expression and clinical significance of RAG1 in myelodysplastic syndromes
Published in Hematology, 2022
Xiaoke Huang, Xiaolin Liang, Shanhu Zhu, Qiongni Xie, Yibin Yao, Zeyan Shi, Zhenfang Liu
Myelodysplastic syndromes (MDS) are a kind of malignant heterogeneous clonal hematological diseases originating from bone marrow hematopoietic stem cells, which are characterized by morphological abnormalities of myeloid cells or multiple myeloid cells, ineffective hematopoiesis. There is a high risk of transformation to acute myeloid leukemia (AML)[1, 2]. The pathogenesis of MDS is very complex, involving abnormal gene expression, gene mutations, epigenetic abnormalities, defects in immune mechanism, and changes in bone marrow microenvironment[1, 3]. With the growth of geriatric population, the incidence of MDS has been increasing, but its clinical treatment is difficult and the cure rate is low. MDS has seriously threatened human health, and there is an urgent need to develop new therapeutic strategies to ameliorate disorders of MDS[4].