Targeted Cancer Treatment (I)

choi

(1)
(a) Philadelphia chromosome
https://en.wikipedia.org/wiki/Philadelphia_chromosome
(section 6 History/ " * * * results in the fusion gene BCR::ABL1.[2] The oncogenic protein with persistently enhanced tyrosine kinase (TK) activity * * * The Philadelphia chromosome is present in the bone marrow cells of a vast majority chronic myelogenous leukemia (CML) patients. * * * The Ph is also observed in patients with acute lymphocytic leukemia (ALL), acute myelogenous leukemia (AML)")
The breakpoint cluster region (BCR) and ABelson murine Leukemia 1 (ABL1) are human genes, so they are italicized and all uppercase (mouse genes will be italicized AND have the first letter capitalized).
BCR codes for protein BCR, whose normal function is unknown. ABL1 encodes ABL1 protein, which is a receptor tyrosine kinase (RTK), which means it is a linear protein with extracellular portion functioning as a receptor, when a ligand binds to the receptor like key and lock, the intracellular portion of tyrosine kinase is activated temporally to phosphorylate tyrosines in its substrates, thereby activating those substrates.

(b) Koretzky GA, The legacy of the Philadelphia chromosome. Journal of Clinical Investigation, 117: 2030 (2007)
https://pmc.ncbi.nlm.nih.gov/articles/PMC1934583/
("In 1960, Peter C Nowell (Figure 1), then a junior faculty member at the University of Pennsylvania School of Medicine, together with a graduate student, David Hungerford, described an unusual small chromosome present in leukocytes from patients with chronic myelogenous leukemia (CML) (1). This abnormality, designated the Philadelphia chromosome after the city in which it was discovered (2), was not found in normal leukocytes but was present in the malignant cells of CML patients")
(i)
(A) The "unusual small chromosome" is what they found. They did not know why (it was so small), much less chromosomal translocation between chromosomes 9 and 22.
(B) The Philadelphia Chromosome: History and Implications for the Future. Fox Chase Cancer Center, Temple University, undated
https://www.foxchase.org/about-u ... adelphia-chromosome
("The seminal discovery took place under a Fox Chase Cancer Center [the Center was created in 1974 through merger' s discovery was done actually in pne of Center's predecessors] microscope in 1959, when David A. Hungerford, in collaboration with Peter C Nowell, detected a tiny abnormality in the chromosomes from cultured blood cells taken from two patients with chronic myelogenous leukemia (CML). This chromosomal abnormality would later be known as the 'Philadelphia Chromosome,' the first consistent chromosome abnormality associated with neoplasia.   Hungerford, at the time of discovery, was a junior research fellow at Fox Chase, pursuing research toward a PhD at the University of Pennsylvania, which he was awarded in 1961. * * * At the time, techniques for preparing chromosomes for microscopic study were still crude. Past researchers had found no abnormal chromosomes in cells from patients with CML, so Hungerford and Nowell presented their new evidence cautiously, in the Journal of National Cancer Institute in 1960. * * * Janet D Rowley discovered the existence of a translocation between chromosomes 9 and 22 in CML in 1973")

At the time associate professor at Department of Hematology, University of Chicago, Janet D Rowley deployed Giemsa stain
https://en.wikipedia.org/wiki/Giemsa_stain
-- developed in 1904; rendering banding pattern of chromosomes -- to pinpoint chromosomal translocation. She did not know what genes were involved at the translocation (as 1973 was at the dawn of DNA sequencing: American Walter Gilbert reported chemical method (if DNA sequencing) that year, to be followed in 1975 by Englishman Frederick Sanger's enzymatic method.
(ii)
(A) Fox Chase is now a neighborhood in City of Philadelphia, from which the cancer center got the name. The neighborhood got its name from Fox Chase Inn (1705-1940), which had been located in Lower Dublin Township, Pennsylvania. Philadelphia annexed the Township in 1854. See Alexander Cutler, Fox Chase; Learn about the history, environment, and business of a small Philadelphia suburb. ArcGIS, May 22, 2024.
https://storymaps.arcgis.com/sto ... 4e589c6d96a79e251c5
(B) ArcGIS
https://en.wikipedia.org/wiki/ArcGIS

(c) treating leukemia caused by Philadelphia chromosome
(i) imatinib
https://en.wikipedia.org/wiki/Imatinib
("sold under the brand names Gleevec * * * (marketed worldwide by Novartis)"/ section 8 History: "The drug received FDA approval in May 2001")
Englishman Nicholas B Lydon, PhD at (Swiss) Ciba-Geigy and Brian J Druker, MD of Oregon Health & Science University developed STI-571, later renamed imatinib (Gleevec). The drug entered in 1998 a phase 1 of clinical trial, partially funded by National Cancer Institute of United States.
(ii) imatinib (etymology)
https://en.wiktionary.org/wiki/imatinib