Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers seek alternative for leukemia patients resistant to standard therapies

04.04.2006


A study led by researchers from the Howard Hughes Medical Institute has found that dasatinib provides significant benefit in chronic myeloid leukemia (CML) patients resistant to Gleevec® (imatinib), according to a study presented today during the 97th Annual Meeting of the American Association for Cancer Research.



In an update of a phase I study initiated in November 2003, researchers looked at the use of dasatinib in imatinib resistant or intolerant patients with CML in late chronic phase (CP), accelerated phase (AP), myeloid blast crisis (MBC), or lymphoid blast crisis (LBC/Ph+ ALL). Data are available for 84 patients (40 CP, 11 AP, 23 MBC, 10 LBC/Ph+ ALL). A blast crisis is the progression of diseases to an acute advanced phase.

Imatinib – which blocks the irregular protein that allows the overproduction of abnormal white blood cells – has become a standard therapy for CML patients not undergoing stem cell transplantation. However, a number of patients have developed resistance to this treatment because their cancer cells are able to mutate and adapt.


The 40 CP patients, with five years median duration of CML, were treated with 15 to 180 mg of dasatinib either once daily (QD) or twice daily (BID) for a median of 13 months. The rate of complete hematologic response (CHR) in CP patients was 93 percent, while major cytogenetic responses (MCyR) were observed in 45 percent and complete cytogenetic response (CCyR) in 35 percent.

In advanced disease, 44 patients have been treated with dasatinib (50 to 240 mg BID) for a median of 37 months. The rate of major hematologic response (MHR) is 81 percent in AP, 61 percent in MBC, and 80 percent in LBC/Ph+ ALL. The overall rates of MCyR and CCyR in advanced disease were 43 percent and 25 percent, respectively. Responses were durable in CP and AP patients, but relapses have occurred in the MBC and LBC/Ph+ ALL groups, often due to dasatinib-resistant BCR-ABL mutations.

CML is usually diagnosed by finding what is called the Philadelphia chromosome (Ph chromosome). The Ph chromosome is the result of a genetic abnormality among portions of chromosomes 9 and 22. In this, part of the BCR (breakpoint cluster region) gene from chromosome 22 is merged with part of the ABL (abelson leukemia virus) gene on chromosome 9. The irregularity takes place in a single bone marrow cell and – through the process of cell division and expansion – results in leukemia, including some cases of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Imatinib resistance in CML and Ph chromosome positive ALL is frequently associated with BCR-ABL mutations that interfere with the ability of imatinib to stop BCR-ABL overproduction. Dasatinib (BMS-354825), which targets BCR-ABL, is 325-fold stronger than imatinib in cells with normal BCR-ABL genes and has demonstrated preclinical activity against 18 of 19 imatinib-resistant BCR-ABL mutants.

*Abstract No. CP-2: Development of the ABL Kinase Inhibitor, Dasatinib (BMS-354825), in Imatinib-Resistant Philadelphia Chromosome Positive Leukemias

Warren Froelich | EurekAlert!
Further information:
http://www.aacr.org

More articles from Studies and Analyses:

nachricht Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University

nachricht New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Developing reliable quantum computers

International research team makes important step on the path to solving certification problems

Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...

Im Focus: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Stiffness matters

22.02.2018 | Life Sciences

Magnetic field traces gas and dust swirling around supermassive black hole

22.02.2018 | Physics and Astronomy

First evidence of surprising ocean warming around Galápagos corals

22.02.2018 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>