Leukaemia cells have a remembrance of things past
Although people generally talk about "cancer", it is clear that the disease occurs in a bewildering variety of forms. Even single groups of cancers, such as those of the white blood cells, may show widely differing properties. How do the various cancers arise and what factors determine their progression? Clues to these two issues, at least for leukaemias, have now been provided by Boris Kovacic and colleagues at the University of Veterinary Medicine, Vienna (Vetmeduni Vienna). The results are published in the current issue of the journal EMBO Molecular Medicine and have extremely important consequences for the treatment of a particularly aggressive type of leukaemia.
It is well known that many types of cancer arise as a result of a mutation within a cell and prevailing wisdom has held that the stage of differentiation of this cell determines exactly what form of cancer develops. For example, it was believed that so-called chronic myeloid leukaemia or CML arises from bone marrow stem cells, while a different type of leukaemia, known as B-cell acute lymphoid leukaemia or B-ALL, results from B-cell precursors. This belief has been spectacularly refuted by the latest results from Boris Kovacic and colleagues in the Vetmeduni Vienna's institutes of Animal Breeding and Genetics and of Pharmacology and Toxicology.
The researchers have now shown that both CML and B-ALL arise from the most primordial kind of blood cell (long-term haematopoietic stem cells), although the pathways by which the diseases progress are different. The usual causes of CML and B-ALL are two highly related versions of the same oncogene, BCR/ABL. If the primordial blood cells are transformed or made potentially cancerous by a particular version of BCR/ABL, for technical reasons termed BCR/ABLp210, the result is chronic myeloid leukaemia or CML. The long-term haematopoietic stem cells remain and act as the dreaded cancer stem cells, or CSCs, which ensure that the disease persists. Curing chronic myeloid leukaemia requires the complete elimination of the CSCs. However, if the long-term haematopoietic stem cells are transformed by a related version of BCR/ABL, BCR/ABLp185, the result is a highly aggressive form of leukaemia, B-ALL. The finding that B-ALL actually originates from the same stem cells as CML was both unexpected and highly provocative.
Kovacic and colleagues have shown further that B-ALL only develops if the transformed stem cell is exposed to a particular growth factor, interleukin-7. If interleukin-7 is present (it usually is), the transformed long-term haematopoietic stem cells undergo a differentiation step to CSCs, which in this case correspond to pro-B cells. If interleukin-7 is absent during the initial phase of transformation, B-ALL cannot develop.
In other words, two distinct types of cell are involved in leukaemia development, the primordial cells (also termed the cells of origin of cancer) and the cancer stem cells that cause the disease to progress. Unless the CSCs are eliminated, fresh cancer cells can arise at any time and the leukaemia will recur. The problem is that current leukaemia therapies are not designed to target CSCs. The primordial CSCs in CML are highly quiescent and thus difficult to target. In contrast, the CSCs in B-ALL are abundant and have a high turnover rate, which makes them susceptible to treatment. Treatment of B-ALL may thus succeed in eliminating most CSCs but if even a single cell remains intact it is likely that the patient will relapse, possibly with an even more aggressive form of leukaemia. "A therapy that targets the bulk of tumour cells will not work," as Kovacic succinctly summarizes his results. "To treat B-ALL successfully it will be necessary for us to learn much more about the development of the disease. A combined therapy is required, so future work should aim at developing drugs that target the long-term haematopoietic stem cells from which B-ALL is derived."
More information: The paper "Diverging fates of cells of origin in acute and chronic leukemia" by Boris Kovacic, Andrea Hoelbl, Gabriele Litos, Memetcan Alacakaptan, Christian Schuster, Katrin M. Fischhuber, Marc A. Kerenyi, Gabriele Stengl, Richard Moriggl, Veronika Sexl and the late Hartmut Beug is published in the current issue of the journal EMBO Molecular Medicine (2012, Vol. 4 pp. 283-297). onlinelibrary.wile… 1100208/full
Provided by University of Veterinary Medicine -- Vienna
- Jak of all trades? Not of leukaemia therapy Jan 30, 2012 | not rated yet | 0
- Targeting leukemia cell's gene 'addiction' presents new strategy for treatment Mar 03, 2010 | not rated yet | 0
- Scientists discover how to beat resistance to standard leukaemia drug Dec 09, 2011 | not rated yet | 0
- Stem cell treatment to prevent leukemia returning is a step closer, say scientists Jun 02, 2011 | not rated yet | 0
- An unexpected way to cause leukemia Apr 07, 2008 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
Use of the newer, more expensive intensity-modulated radiotherapy (IMRT) and use of the older conformal radiotherapy (CRT) after surgical removal of all or part of the prostate gland were associated with similar morbidity ...
Cancer 34 minutes ago | not rated yet | 0
New research suggests that a compound abundant in the Mediterranean diet takes away cancer cells' "superpower" to escape death. By altering a very specific step in gene regulation, this compound essentially re-educates cancer ...
Cancer 54 minutes ago | 5 / 5 (1) | 0 |
(HealthDay)—For young adults needing either a chest or abdominopelvic computed tomography (CT), the short-term risk of death from underlying morbidity is greater than the long-term risk of radiation-induced ...
Cancer 2 hours ago | not rated yet | 0
In a new study described in the journal Oncogene, researchers reveal how a key player in cell growth, immunity and the inflammatory response can be transformed into a primary contributor to tumor growth.
Cancer 7 hours ago | not rated yet | 0 |
A new study conducted using extensive medical records of over one million Israeli adolescents before military service shows clearly how exposure to the Israeli sun of young, light-skinned children increases substantially ...
Cancer 9 hours ago | not rated yet | 0
(Medical Xpress)—Individuals who learn two languages at an early age seem to switch back and forth between separate "sound systems" for each language, according to new research conducted at the University of Arizona.
28 minutes ago | not rated yet | 0 |
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
14 minutes ago | not rated yet | 0 |
Discovery of circadian clock in mice hair reveals period of time when damage from radiotherapy can be quickly repaired
Discovering that mouse hair has a circadian clock - a 24-hour cycle of growth followed by restorative repair - researchers suspect that hair loss in humans from toxic cancer radiotherapy and chemotherapy ...
41 minutes ago | not rated yet | 0 |
A Saudi man who had contracted the coronavirus has died, raising the death toll in the kingdom from the SARS-like virus to 16, the health ministry announced on Monday on its Internet website.
14 minutes ago | not rated yet | 0
Little is known about the effect of physical education (PE) on child weight, but a new study from Cornell University finds that increasing the amount of time that elementary schoolchildren spent in gym class reduces the probability ...
28 minutes ago | not rated yet | 0
Video games that pit players against human-looking characters may be more likely to provoke violent thoughts and words than games where monstrous creatures are the enemy, according to a new study by researchers ...
30 minutes ago | not rated yet | 0