Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Researchers identify cells that make relapse inevitable after treatment for acute lymphoblastic leukaemia

In “Dr Jekyll and Mr Hyde” Robert Louis Stevenson wrote about the good and evil sides of the same person; now scientists in Australia have discovered that in acute lymphoblastic leukaemia (ALL) there are Dr Jekyll and Mr Hyde cells – “good” and “evil” clones of the same type of ALL cell.

The “evil” cells are clones that have a pre-existing, rather than acquired, resistance to drugs used for treating ALL, and their presence in a patient means that person will inevitably relapse after chemotherapy, however well they respond initially.

The discovery means that now researchers may be able to design therapies that will specifically target these resistant subclones so that, in the future, patients who have been identified as having them can be treated immediately with the alternative therapies.

ALL is the most common cancer in children and, although nearly all patients will respond initially to chemotherapy, one in four will relapse. Seoyeon Choi told the EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics in Prague today (Thursday 9 November): “We have previously shown that these relapses were due to small numbers of surviving and highly drug refractory cells. However, until now, it has been unclear whether these relapses resulted from the acquisition of therapy-induced drug resistance or were caused by a subpopulation of cells that were already intrinsically drug resistant.”

... more about:
»ALL »Choi »identify »inevitable »leukaemia »relapse »therapies

Ms Choi, a final year PhD student at the Children’s Cancer Institute Australia in Sydney and medical student at the University of Sydney, Australia, analysed samples taken from 25 ALL patients at the time of their diagnosis and at their relapse to discover the molecular “fingerprint” of every ALL cell.

“White blood cells, or lymphocytes, are unique in that every one has its own molecular signature. Therefore, we can ‘molecular fingerprint’ each lymphocyte in order to know what the leukaemia ‘looks’ like. We found ‘fingerprints’, or clonal markers, that revealed the emergence or evolution of new clonal populations at the time of relapse in 13 patients. In eight of the samples, highly sensitive clone-specific PCR [polymerase chain reaction] revealed that these ‘relapse’ clones had been present in small numbers at the time of diagnosis, indicating that they were involved in the mechanism of relapse.

“My research indicates that these are not different leukaemias, but a smaller population of related cells that are naturally more aggressive than the major clone. The problem is that they are present at such low levels, hidden behind the obvious leukaemia; the patient would appear to be responding well to treatment with the major leukaemia clones dying, but, in fact, the small number of subclones can survive therapy and cause a relapse.”

The researchers found that the presence of the subclone at diagnosis correlated significantly with the length of the first clinical remission, and the more of the subclone that was present, the quicker the patient relapsed.

Ms Choi said: “I believe it is important to know that these cells are actually more resistant and aggressive from the very beginning, like a evil twin, if you like. While the ‘good’ twin, or the major clone, appears to be responding well – and lulling the clinicians into a false sense of security – the ‘evil’ twin, or subclone that is identified too late because of their small numbers, can cause relapse, by which time they are present in very high numbers. Knowing this, we can identify such patients early on in their treatment and focus on new therapies that target the right cell/clonal population so that we may be able to improve the outcome for this special group of patients who relapse early.

“Patients who relapse early usually have a particularly poor outcome, and if we could prevent the relapse that is inevitable under the current treatment regime, then we might be able to make a big difference to these children’s survival.”

The researchers believe that, in those patients where they were unable to detect subclones, the cells may have existed, but in numbers too low to be detected by current methods, and they are working to improve the PCR technique in order to increase its sensitivity so that it can be used to identify even smaller numbers of subclones.

At present there are no therapies that can be used specifically to treat children who are identified as having the relapse subclone. However, Ms Choi said that now her research had identified the cells that made relapse inevitable, it would be possible for researchers to start work on therapies that could target these cells. “If we could treat these differently, by targeting them early in therapy, or introducing alternative therapies, we may improve the overall outcome of every patient with leukaemia.

“While I do not know when this research will translate into clinical changes, I do believe that it will happen in my lifetime when I graduate from medical school and start to practice as a physician.”

1.EORTC [European Organisation for Research and Treatment of Cancer, NCI [National Cancer Institute], AACR [American Association for Cancer Research].

Emma Mason | alfa
Further information:

Further reports about: ALL Choi identify inevitable leukaemia relapse therapies

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>