China
Africa
Explore chapters and articles related to this topic
L
Published in Anton Sebastian, A Dictionary of the History of Medicine, 2018
Leukemia [Greek: leukos, white + haima, blood] Term used for the cellular disorder of blood was first coined by Rudolph Virchow (1821–1902) in 1845, and the first description was given by John Hughes Bennett (1812–1875) in the same year. Bennett later published a monograph on leucocythemia in 1852 in which he showed the microscopic blood picture in leukemia. Radioactive isotopes were employed for the first time in the treatment by John Hundale Lawrence (b 1904) and co-workers in 1939. See bone marrow transplant, chronic myeloid leukemia.
The e1a3 BCR-ABL1 fusion transcript in Philadelphia chromosome-positive acute lymphoblastic leukaemia: a case report
Published in Hematology, 2023
The abnormal Philadelphia (Ph) chromosome is formed by the mutual translocation between chromosomes 9 and 22 (t [9; 22], [q34; q11.2]); the formation of the breakpoint cluster region-Abelson murine leukaemia 1 (BCR-ABL1) fusion gene is its main molecular biological feature [1]. The protein encoded by the BCR-ABL1 fusion gene has abnormally high tyrosine kinase activity [2]. This acquired gene rearrangement is most classically associated with chronic myeloid leukaemia (CML), but it has also been found in acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) cases [3]. The presence of the BCR-ABL1 transcript in ALL is associated with a relatively poor prognosis and low sensitivity to chemotherapy. The three typical BCR-ABL1 mRNA transcripts are e1a2, e13a2 and e14a2; other rare variants, such as e1a3, b2a3 and e6a2, have also been reported [4,5]. However, these observations were made almost exclusively in CML cases [6], and very little is known about atypical transcripts in Ph chromosome–positive (Ph+) ALL. In this paper, the clinical course of a rare case of Ph+ ALL with an e1a3 BCR-ABL1 fusion transcript is reported.
Stachydrine is effective and selective against blast phase chronic myeloid leukaemia through inhibition of multiple receptor tyrosine kinases
Published in Pharmaceutical Biology, 2022
Ruixin Gu, Wei Zhang, Dandan Xu
Chronic myeloid leukaemia (CML) is a haematopoietic malignancy caused by the presence of the fusion gene BCR-ABL in stem/progenitor cells (Sawyers 1999). BCR-ABL encodes a constitutively active tyrosine kinase that leads to upregulation of signal transduction pathways involved in cell survival and growth, such as Ras/MEK/MAPK and PI3K/AKT (Ren 2005). The introduction of BCR-ABL tyrosine kinase inhibitors (TKIs, e.g., imatinib, dasatinib and ponatinib) that bind to the ATP-binding site of Abl, has led to a remarkable clinical response to treat CML. However, patients develop resistance to TKIs and progress to blast phase (BP). Mutations in the Abl kinase domain and Bcr-Abl protein overexpression are the main mechanisms that contribute to TKI resistance (Perrotti et al. 2010; Corbin et al. 2011). Therefore, identification of agents that overcome TKI resistance is needed to improve clinical response in blast phase chronic myeloid leukaemia (BP-CML) patients.
Synthesis and biological activity evaluation of 3-(hetero) arylideneindolin-2-ones as potential c-Src inhibitors
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Salvatore Princiotto, Loana Musso, Fabrizio Manetti, Valentina Marcellini, Giovanni Maga, Emmanuele Crespan, Cecilia Perini, Nadia Zaffaroni, Giovanni Luca Beretta, Sabrina Dallavalle
In this context, many efforts have been made to design and discover new molecules acting as c-Src inhibitors, blocking its downstream pathways and impairing tumour progression24–27. To date, five molecules targeting Src have been approved by FDA (Figure 2), and several others are in clinical trials for the treatment of solid tumours and leukemias, often in association with other cytotoxic agents. In particular, Dasatinib and Bosutinib have been approved for the treatment of chronic myeloid leukaemia (CML) in adult and paediatric patients28,29. Saracatinib, characterised by a more selective profile in terms of Src family inhibition30, is in clinical trials for the treatment of several solid tumours24. Vandetanib and Ponatinib are multi-tyrosine kinase inhibitors, approved by FDA to treat CML, thyroid carcinoma, and Philadelphia chromosome-positive acute lymphoblastic leukaemia in adults31,32. Other promising c-Src inhibitors (in phase I or II, (Figure 2) are DGY-06–11633, eCF50634, Elzovantinib (TPX-0022)35, and Tirbanibulin, the latter targeting the Src substrate binding site36 and recently approved for the topical treatment of actinic keratosis37.