Researchers have identified a second path to defeating chronic myelogenous leukemia, which tends to affect older adults, even in the face of resistance to existing drugs. The new findings were published in Nature Communications.
Almost all patients with chronic myelogenous leukemia, or CML, have a faulty, cancer-causing gene, or "oncogene" called BCR-ABL1. BCR-ABL1 turns a regular stem cell (a unique type of cell that can turn into other types of cells and then reproduce those cells during life time) in the bone marrow into a CML stem cell that produces malformed blood cells. And instead of the CML stem cell dying when it should be scheduled to do so, the oncogene causes it to keep producing even more of these faulty blood cells.
Advances in treatment since the turn of the millennium have been extremely successful at combatting the disease in patients with this oncogene. Drugs called tyrosine kinase inhibitors (TKI) have completely transformed the prognosis of people with such leukemias, and with fewer of the side effects of other cancer treatments. In most cases, the cancer goes into remission and patients live for many years following diagnosis.
BCR-ABL1 directs the production of an abnormal type of tyrosine kinase, an enzyme that 'turns on' many types of proteins through a cascade of chemical reactions known as signal transduction--in effect communication via chemistry. Miscommunication resulting from the faulty enzyme is what promotes the growth of the leukemic cells. By stopping this communication within CML stem cells, TKI signal transduction therapy inhibits their growth and brings a halt to their production of the malformed blood cells.
However, TKIs only controls the disease; they don't cure it. Drug resistance can develop in a patient because while TKIs work well on proliferative mature CML cells that are actively reproducing, they are less effective at inducing cell death on the part of CML stem cells that are quiescent.
Quiescence is an "idling" stage in the life cycle of a cell in which it basically just rests and hangs out for extended periods of time in anticipation of reactivation, neither replicating nor dying.
"If CML stem cells are in a quiescent phase, they are otherwise left untouched by TKI treatment, and so survive to potentially cause a relapse," said the senior author.
But the researchers found in mouse models that if they disrupt Gdpd3--a different, non-oncogene gene--then the self-renewal capacity of the CML stem cells is sharply decreased. Gdpd3 directs the production of an enzyme for a particular type of lipid that appears to play a key role in regulating the quiescence of CML stem cells in an oncogene-independent fashion.
In other words, the Gdpd3 gene involved in production of this lipid is largely responsible for the maintenance of CML stem cells. The researchers had broken their quiescence.
Crucially, when the researchers disrupted the Gdpd3 gene encoding these lipids, leukemia relapse in the mice was significantly reduced, even when the BCR-ABL1 oncogene was not disrupted.
"This potentially provides another path to arresting these leukemias--and maybe other cancers too," said the author, "beyond having to wrestle with the BCR-ABL1 oncogene."
While the researchers have discovered a new, biologically significant role for this particular lipid in causing the recurrence of CML, they still do not fully understand the precise way this happens. The researchers now want to investigate the mechanisms involved and whether this lipid also plays a role in the quiescence of the cancer stem cells that cause solid tumors, not just in leukemias, and thus in these cancers' recurrence and growth as well.
https://www.hiroshima-u.ac.jp/en/news/60227
https://www.nature.com/articles/s41467-020-18491-9
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fthe-lysophospholipase-d&filter=22
Role of lipids in leukemia relapse
- 1,010 views
- Added
Edited
Latest News
TB blood test which could d…
By newseditor
Posted 27 Mar
Propionate supplementation…
By newseditor
Posted 27 Mar
Role of human Kallistatin i…
By newseditor
Posted 26 Mar
Addressing both flu and COV…
By newseditor
Posted 26 Mar
How the brain senses body p…
By newseditor
Posted 26 Mar
Other Top Stories
Predicting fruit fly stripe formation during embryonic development
Read more
Extending lifespan of mice with CRISPR-CAS9 gene therapy
Read more
Gene therapy for congenital deafness
Read more
Gene variants that significantly influence how the body distributes…
Read more
A microRNA mutation results in skeletal muscle disease!
Read more
Protocols
All-optical presynaptic pla…
By newseditor
Posted 23 Mar
Epigenomic tomography for p…
By newseditor
Posted 20 Mar
A mouse DRG genetic toolkit…
By newseditor
Posted 17 Mar
An optogenetic method for t…
By newseditor
Posted 13 Mar
Profiling native pulmonary…
By newseditor
Posted 08 Mar
Publications
Integrated plasma proteomic…
By newseditor
Posted 27 Mar
APP antisense oligonucleoti…
By newseditor
Posted 27 Mar
Targeting Erbin-mitochondri…
By newseditor
Posted 27 Mar
Regulation of Zbp1 by miR-9…
By newseditor
Posted 27 Mar
Pain-free oral delivery of…
By newseditor
Posted 27 Mar
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar