A Worldwide Support Network For Chronic Myelogenous Leukemia
Posted by rob on December 19, 2005 under Uncategorized | 
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The days of the Raj are long gone, but multinational corporations are riding high on the trend toward globalization by taking advantage of India’s educated work force and deep poverty to turn South Asia into the world’s largest clinical-testing petri dish.
Posted by rob on December 17, 2005 under Uncategorized | Be the First to Comment
Chandra J, Tracy J, Loegering D, Flatten K, Verstovsek S, Beran M, Gorre M, Estrov Z, Donato N, Talpaz M, Sawyers C, Bhalla K, Karp J, Sausville E, Kaufmann SH
Blood. 2005 Nov 15;
The bcr/abl kinase has been targeted for the treatment of chronic myelogenous leukemia (CML) by imatinib mesylate. While imatinib has been extremely effective for chronic phase CML, blast crisis CML and Ph+ ALL are often resistant. In particular, mutation of the T315 residue in the bcr/abl activation loop renders cells highly resistant to imatinib and to second-generation kinase inhibitors such as BMS354825 or AMN107. Adaphostin is a tyrphostin that was originally intended to inhibit the bcr/abl kinase by competing with its peptide substrates. Recent findings have, in addition, implicated the capacity to generate reactive oxygen species (ROS) in the cytotoxic mechanism of adaphostin. In view of this unique mode of action, we examined the effects of adaphostin on numerous imatinib-resistant leukemia models, including imatinib-resistant CML and Ph+ ALL cell lines, cells harboring point mutations in bcr/abl, and specimens from imatinib-resistant CML patients, using assays for intracellular ROS, apoptosis and clonogenicity. Every cell line model of imatinib resistance examined remained fully sensitive to adaphostin-induced cell death. Collectively, these data suggest that ROS generation by adaphostin overcomes even the most potent imatinib resistance in CML and Ph+ ALL.
Adaphostin-induced oxidative stress overcomes bcr/abl mutation-dependent and -independent imatinib resistance.
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Miyoshi N, Tanaka H, Ito T, Katayama Y, Niimi H, Hyodo H, Kimura A
Int J Hematol. 2005 Nov ; 82(4): 333-7
The case of a 72-year-old woman with chronic myelogenous leukemia in blast phase (BP) with hypercalcemia is reported. Bone x-ray examination revealed multiple osteolytic lesions throughout the body. The serum level of parathyroid hormone-related protein (PTHrP) was elevated, and PTHrP messenger RNA (mRNA) was detectable in the peripheral blood mononuclear cells (PBMNC) at BP but was not detectable at chronic phase (CP).Treatment with conventional chemotherapy did not completely control either serum calcium level or serum PTHrP level. Treatment with imatinib mesylate (imatinib) alone rapidly normalized these parameters in parallel with a decrease in the number of blast cells. The treatment also maintained the patient in good condition for approximately 3 months, even though the number of blast cells, serum calcium level, serum PTHrP level, and PTHrP mRNA level increased at the terminal stage. Mutations of the p53, K-Ras, and BCR-ABL genes in PBMNC at BP were absent. A noteworthy feature in this patient was that PBMNC at BP but not at CP showed high Lyn mRNA expression. Taken together the findings showed that production of PTHrP by blast cells was favorably controlled by imatinib therapy alone. Imatinib may prolong survival time at BP even though the patients have the complication of PTHrP-mediated hypercalcemia.
Use of imatinib mesylate for favorable control of hypercalcemia mediated by parathyroid hormone-related protein in a patient with chronic myelogenous leukemia at blast phase.
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Millot F, Guilhot J, Nelken B, Leblanc T, Leverger G, Bernard F, Gandemer V, B?hard C, Berger C, Cornu G, Duch?ne S, Guilhot F
Pediatr Blood Cancer. 2005 Nov 29;
BACKGROUND: Chronic myelogenous leukemia (CML) is a rare disease in children and only few data are available concerning the results of interferon based therapy in this age group. Before the imatinib mesylate era, a prospective phase II trial was conducted to assess the efficacy and tolerance of a combination of interferon-alpha 2b (IFN) and cytarabine in children with CML in first chronic phase without a suitable HLA-identical donor. PROCEDURE: Fourteen consecutive children were recruited from 12 pediatric centers. Children received daily IFN (5 million U/m(2)) and subcutaneous cytarabine (20 mg/m(2)) for 10 days every month. RESULTS: The median duration of follow-up is 13 months (range 2-32 months). Seven children achieved a complete hematologic response after a median time of treatment of 3 months (range 1 week-4 months). Three children were not evaluable for the cytogenetic response. A major cytogenetic response was achieved in seven patients (including complete cytogenetic response in two patient) within 12 months. The median time to major cytogenetic response was 7 months (range 3-12 months). Thirteen patients discontinued the treatment protocol after a median time of 11 months. Probability of progression free survival at 11 months was 83% (95% CI, 61%-100%). Grade 3 and 4 toxicity was observed in eight patients. The most frequently reported drug-related events were fever, mucositis, neutropenia, and thrombocytopenia. CONCLUSIONS: The combination of IFN and cytarabine provides hematologic and cytogenetic responses in children and adolescents with CML. In the imatinib mesylate era, the role of this combination as second line therapy in children with CML remains to be determined. (c) 2005 Wiley-Liss, Inc.
Results of a phase II trial testing interferon-alpha 2b and cytarabine in children and adolescents with chronic myelogenous leukemia.
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Rousselot P
Rev Prat. 2005 Oct 15; 55(15): 1647-57
Chronic myelogenous leukemia is the main diagnosis in case of primitive hyperleucocytosis ou thrombocytosis. The Philadelphia chromosome could be evidenced in the bone marrow by cytogenetic analysis or in the peripheral blood by amplification of the BCR-ABL fusion gene with RT-PCR. A new targeted therapy, imatinib mesylate (Gleevec), inhibits of the dysregulated kinase activity of BCR-ABL. A complete cytogenetic response defined by the absence of Ph+ chromosome in bone marrow is obtained in 85% of cases at the daily dosage of 400 mg. The response is then monitored by quantification of the BCR-ABL transcript. This apparent simple, orally available and well tolerated therapy need to be carefully monitored by real time quantitative PCR in highly specialized laboratories. Allogenic hematopoietic stem cell transplantation remains a curative approach in case of HLA identical donor and is proposed to young patients or in case of imatinib failure. A second generation of BCR-ABL inhibitors is currently in clinical trial.
[Diagnosis and treatment of chronic myelogenous leukemia]
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Sun J, Huang H, Zhu YY, Lan JP, Li JY, Lai XY, Yu J
J Zhejiang Univ Sci B. 2005 Dec. ; 6(12): 1141-1147
Objective: Detecting the expression and mutation of human telomeric repeat binding factor (hTRF1) in 10 malignant hematopoietic cell line cells on the base of determining its genomic structure and its four pseudogenes to clarify if hTRF1 mutation is one of the factors of the activation of telomerase. Methods: hTRF1cDNA sequences were obtained from GenBank, its genome structure and pseudogenes were forecasted by BLAST and other biology information programs and then testified by sequencing. Real-time RT-PCR was used to detect the expression of hTRF1mRNA in 10 cell line cells, including myelogenous leukemia cell lines K562, HL-60, U-937, NB4, THP-1, HEL and Dami; lymphoblastic leukemia cell lines 6T-CEM, Jurkat and Raji. Telomerase activities of cells were detected by using telomeric repeat amplification (TRAP)-ELISA protocol. PCR and sequencing were used to detect mutation of each exon of hTRF1 in 10 cell line cells. Results: hTRF1 gene, mapped to 8q13, was divided into 10 exons and spans 38.6 kb. Four processed pseudogenes of hTRF1 located on chromosome 13, 18, 21 and X respectively, was named as PsihTRF1-13, PsihTRF1-18, PsihTRF1-21 and PsihTRF1-X respectively. All cell line cells showed positive telomerase activity. The expression of hTRF1 was significantly lower in malignant hematopoietic cell lines cells (0.0338, 0.0108~0.0749) than in normal mononuclear cells (0.0493, 0.0369~0.128) (P=0.004). But no significant mutation was found in all exons of hTRF1 in 10 cell line cells. Four variants were found in part of intron 1, 2 and 8 of hTRF1. Their infection on gene function is unknown and needs further studies. Conclusion: hTRF1 mutation is probably not one of the main factors for telomerase activation in malignant hematopoietic disease.
Study on the expression and mutation of human telomeric repeat binding factor (hTRF1) in 10 malignant hematopoietic cell lines.
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Giles FJ, Cortes JE, Kantarjian HM
Curr Mol Med. 2005 Nov ; 5(7): 615-23
Imatinib mesylate is a major advance in the therapy of patients with chronic myelogenous leukemia (CML). Imatinib mesylate binds to the inactive conformation of BCR-ABL tyrosine kinase suppressing the Philadelphia chromosome positive clone in CML. Clinical studies have yielded impressive results in all phases of CML. With higher rates of complete cytogenetic response with imatinib, molecular monitoring of disease is now advisable in assessing response and determining prognosis. Emergence of resistance to imatinib may be manifest at the hematologic, cytogenetic, or molecular levels in patients who remain in chronic phase, or may be evidenced by the development of more advanced CML phases. Resistance and eventual clinical failure of imatinib occurs in most patients with blastic phase disease. Resistance may occur at the level of Bcr-Abl, with reduction or loss of imatinib effectiveness as a kinase inhibitor, or, despite retention of its inhibitory ability, with changes in the ability to deliver an effective dose at the cellular level, and/or, the leukemia becoming less dependent on Bcr-Abl. The various mechanisms underlying these differing, non-mutually exclusive, mechanisms of resistance must be understood to develop corresponding therapeutic remedies. We review the current data on imatinib in CML, the criteria for diagnosis of imatinib resistance, and the mechanisms that underlie such resistance in CML.
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Deininger M
J Natl Compr Canc Netw. 2005 Nov ; 3(6): 757-68
Imatinib, a specific small molecule inhibitor of the Abl kinase, has become the standard drug therapy for chronic myelogenous leukemia in all phases. More than 80% of newly diagnosed patients with chronic phase attain a complete cytogenetic response (CCR). Although remissions in patients with early disease are generally durable, acquired resistance after an initial response is common in advanced disease. Reactivation of Bcr-Abl signaling is almost invariably present at the time of relapse, consistent with re-establishment of the initial pathogenetic mechanism. Mutations in the kinase domain (KD) of Bcr-Abl that impair drug binding and increased expression of Bcr-Abl have been identified as major mechanism of acquired drug resistance. The fact that Bcr-Abl remains central to disease pathogenesis at the time of relapse implies that it also remains the optimal drug target. Alternative Abl kinase inhibitors with increased potency and activity against most Bcr-Abl KD mutants are currently undergoing phase I/II clinical testing, with encouraging early results. Despite the high rates of CCR, persistence of residual leukemia as assessed by reverse transcription polymerase chain reaction is the rule even in patients with chronic phase, suggesting that even these patients may remain at risk of relapse. Understanding the mechanisms underlying disease persistence will be crucial for developing strategies to eradicate residual leukemia.
Posted by rob on December 15, 2005 under Uncategorized | Be the First to Comment
Two-pronged strategy launches assault on blood cancer
Posted by the Asbury Park Press on 12/14/05
BY LIZ SZABO
USA TODAY
Sometimes, a wonder drug isn’t good enough.
Doctors and patients around the world hailed the approval of Gleevec in 2001, which revolutionized the treatment of chronic myeloid leukemia and marked the beginning of what scientists hope will be a new era in cancer therapy.
Scientists engineered Gleevec to silence growth signals from a rogue protein that causes the blood cancer. Patients who were bedridden have returned to normal ? often staying in remission for years, says Brian Druker, a professor at Oregon Health & Science University who developed Gleevec.
Yet while Gleevec can keep cancer at bay, it doesn’t appear to cure anyone. Patients who stop taking the drug soon relapse. And even apparently healthy patients still harbor hidden reservoirs of cancer, says K.K. Wong, a blood cancer specialist at the City of Hope National Medical Center in Duarte, Calif.
Researchers now are searching for ways to eliminate these stubborn cancer cells. One preliminary, experimental method, presented Saturday at a meeting of the American Society of Hematology in Atlanta, is designed to work with Gleevec like a combined air and ground assault.
The strategy, developed by scientists at the University of Siena in Italy, aims to boost patients’ immune systems to recognize and kill cancer cells, says Druker, who introduced the research Saturday but was not involved in the study. Although scientists still don’t completely understand how the immune system fights cancer, they suspect that the body’s natural defenses routinely clean up abnormal cells such as cancers.
APP.COM v4.0 – Two-pronged strategy launches assault on blood cancer | Asbury Park Press Online
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WEDNESDAY, Dec. 14 (HealthDay News) — Nearly five years on, 90 percent of patients with a form of leukemia are alive and free of disease after taking the drug Gleevec (imatinib), according to updated trial results.
At 4.5 years, nine out of 10 patients with the common, Philadelphia chromosome-positive form of chronic myeloid leukemia (CML) were still alive and their yearly risk of progressing to advanced disease was less than 1 percent, according to a study presented this week at the American Society of Hematology annual meeting in Atlanta.
The findings come from a Phase III retrospective comparison of Gleevec and interferon-based treatment that included more than over 1,100 newly diagnosed patients. The patients were treated at 177 centers in 16 countries.
One group of patients was assigned to receive 400 milligrams per day of Gleevec, with a second group of patients receiving interferon (IFN) 5 MIU M2 per day with Ara-C 20 mg/M2/day for 10 days each month.
After 36 months of treatment, the overall survival rate for the patients taking Gleevec was 92 percent, compared to 84 percent for patients receiving IFN and Ara-C. After 54 months, the Gleevec patients had an overall survival rate of 90.3 percent.
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Trial shows long term benefit of Novartis leukemia drug Gleevec | CMLHope.Com | Bringing Hope To CML
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Bornh?user M, Kr?ger N, Schwerdtfeger R, Schafer-Eckart K, Sayer HG, Scheid C, Stelljes M, Kienast J, Mundhenk P, Fruehauf S, Kiehl MG, Wandt H, Theuser C, Ehninger G, Zander AR,
Eur J Haematol. 2006 Jan ; 76(1): 9-17
Objective: To analyse the results of allogeneic haematopoietic cell transplantation (HCT) in patients with advanced stages of Philadelphia chromosome-positive chronic myelogenous leukaemia (CML) who had previously been treated with imatinib mesylate (IM). Methods: We analysed the outcome of 61 patients with CML who had received allogeneic HCT from sibling (n = 18) or unrelated (n = 43) donors after having been treated with IM. Forty-one patients had received IM because of accelerated or blast phase CML. Conditioning therapy contained standard doses of busulfan (n = 25) or total-body irradiation (n = 20) in conjunction with cyclophosphamide in the majority of cases. Sixteen patients received dose-reduced conditioning with fludarabine-based regimens. Results: The incidence of grades II-IV and III-IV graft-versus-host disease was 66% and 38% respectively. The probability of overall survival (OS), disease-free survival (DFS) and relapse at 18 months for the whole patient cohort were 37%, 33% and 24% respectively. The probability of non-relapse mortality (NRM) at 100 d and 12 months was 30% and 46% respectively. Univariate analysis showed that fludarabine-based conditioning therapy, age >/=40 yr and >12 months interval between diagnosis and transplantation were associated with a significantly lower OS and DFS and a higher NRM. Conclusion: These data suggest that although pretreatment with IM is not an independent negative prognostic factor, it cannot improve the dismal prognosis of CML patients at high risk for transplant-related mortality.
Allogeneic haematopoietic cell transplantation for chronic myelogenous leukaemia in the era of imatinib: a retrospective multicentre study.
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Borthakur G, Kantarjian H, Daley G, Talpaz M, O’brien S, Garcia-Manero G, Giles F, Faderl S, Sugrue M, Cortes J
Cancer. 2005 Dec 8;
BACKGROUND: Lonafarnib (SCH66336) is a nonpeptidomimetic farnesyl transferase inhibitor that has demonstrated significant preclinical activity against chronic myelogenous leukemia (CML) cells and in CML animal models. METHODS: In the current study, the efficacy of lonafarnib was investigated in patients with CML in the chronic or accelerated phase that was resistant or intolerant to imatinib. Thirteen patients with CML in the chronic (n = 6 patients) or accelerated (n = 7 patients) phase were treated with lonafarnib at a dose of 200 mg orally twice daily. Ten patients had failed therapy with imatinib and 3 patients were intolerant to imatinib. The median age of the patients was 62 years (range, 38-80 yrs) and the median time from the diagnosis of CML to therapy with lonafarnib was 5 years (range, 0.3-13 yrs). In addition to imatinib mesylate, all patients had received prior therapy with interferon-alpha and seven patients had received other treatments. The median duration of therapy with lonafarnib was 8 weeks (range, 2-41 wks). RESULTS: Two patients responded. One patient in the accelerated phase of CML returned to the chronic phase, a response that lasted for 3 months. Another patient with chronic phase disease had lowering of the leukocyte count without the need for hydroxyurea and normalization of the differential count that lasted for 5 months. The most common adverse event was diarrhea, which was noted in 11 patients (84%) (Grade >/= 3 in 4 patients; 31%; toxicity was graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]). Therapy was discontinued in one patient because of diarrhea not responding to dose adjustments. CONCLUSIONS: Single-agent lonafarnib appears to have clinical activity in a small proportion of patients with CML refractory to imatinib. Cancer 2006. (c) 2005 American Cancer Society.
Pilot study of lonafarnib, a farnesyl transferase inhibitor, in patients with chronic myeloid leukemia in the chronic or accelerated phase that is resistant or refractory to imatinib therapy.
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Millot F, Guilhot J, Nelken B, Leblanc T, De Bont ES, B?kassy AN, Gadner H, Sufliarska S, Stary J, Gschaidmeier H, Guilhot F, Suttorp M
Leukemia. 2005 Dec 8;
A multicentric phase 2 study was conducted to determine the efficiency and the tolerance of imatinib mesylate in children with chronic myelogenous leukemia (CML) in advanced phase of the disease, in relapse after stem cell transplantation, or in case of failure to an interferon alpha-based regimen. In all, 30 children from eight European countries were enrolled. In 18 children assessable for hematologic response, imatinib mesylate induced complete hematologic response in eight (80%) of the 10 patients included in chronic phase and in six (75%) of eight enrolled in advanced phase of the disease with acceptable toxicity. In 27 patients assessable for cytogenetic response, imatinib mesylate induced disappearance of Philadelphia chromosome-positive bone marrow cells in 12 (60%) of 20 children included in chronic phase and in two (29%) of seven included in advanced phase. A reduction of the bcr-abl/abl ratio to less than 10(-4) was achieved in 11 (50%) of the children included in chronic phase. Estimated 12-month overall survival rate was 95% (95% CI, 87-100%) for the patients included in chronic phase and 75% (95%CI, 45-100%) for those enrolled in advanced phase. Imatinib mesylate is well tolerated and molecular remission can be achieved in children with CML.Leukemia advance online publication, 8 December 2005; doi:10.1038/sj.leu.2404051.
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Duplication of the Ph-chromosome as a possible mechanism of resistance to imatinib mesylate in patients with chronic myelogenous leukemia.
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Fugazza G, Garuti A, Marchelli S, Miglino M, Bruzzone R, Gatti AM, Castello S, Sessarego M
Cancer Genet Cytogenet. 2005 Dec ; 163(2): 173-5
The cytogenetic studies and molecular evaluation of a Philadelphia chromosome negative chronic myelogenous leukemia patient with trisomy 21 (100% metaphases) and trisomy 9 (50% metaphases) at diagnosis are described. Fluorescence in situ hybridization revealed an atypical location of the BCR/ABL fusion signal on 9q, which was duplicated in cells with trisomy 9 simulating a double Ph. The patient was successfully treated with Glivec (also known as Gleevec; Novartis, Basel, Switzerland) and achieved complete hematological and cytogenetic response as well as a reduction of BCR/ABL transcripts detected by real-time quantitative PCR.
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Park J, Kim S, Oh JK, Kim JY, Yoon SS, Lee D, Kim Y
J Biochem Mol Biol. 2005 Nov 30; 38(6): 725-38
Resistance to imatinib mesylate (also known as Gleevec, Glivec, and STI571) often becomes a barrier to the treatment of chronic myelogenous leukemia (CML). In order to identify markers of the action of imatinib mesylate, we used a mass spectrometry approach to compare protein expression profiles in human leukemia cells (K562) and in imatinib mesylate-resistant human leukemia cells (K562-R) in the presence and absence of imatinib mesylate. We identified 118 differentially regulated proteins in these two leukemia cell-lines, with and without a 1 microM imatinib mesylate challenge. Nine proteins of unknown function were discovered. This is the first comprehensive report regarding differential protein expression in imatinib mesylate-treated CML cells.
Identification of differentially expressed proteins in imatinib mesylate-resistant chronic myelogenous cells.
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Yang F, Zhang Y, Cao YL, Wang SH, Liu L
Acta Biochim Biophys Sin (Shanghai). 2005 Dec ; 37(12): 851-6
RNA interference (RNAi), a posttranscriptional gene silencing process mediated by small double-stranded RNA specifically complementary to the targeted transcript, has been used extensively in the development of novel therapeutic approaches against various human diseases including chronic myelogenous leukemia (CML). Here, we report the successful construction of a tetracycline-controlled siRNA in CML cell line K562. A K562 cell line stably expressing the reverse tetracycline-controlled transactivator (rtTA) was constructed. A tetracycline responsive element (TRE) was integrated into the RNA polymerase III promoter region of pBS/U6 that was used to drive specific siRNA to target the novel cytokine receptor-like factor 3 (CRLF3) gene. The results show that rtTA was able to recognize the TRE to prevent siRNA-mediated exogenous and endogenous CRLF3 gene repressions. Moreover, CRLF3-siRNA mediated gene repression could be induced in a dose-dependent manner in the presence of doxycycline. Thus, the inducible siRNAi system in K562 cells might be useful for the study of RNAi-mediated therapeutic approaches against CML.
Establishment and Utilization of a Tetracycline-controlled Inducible RNA Interfering System to Repress Gene Expression in Chronic Myelogenous Leukemia Cells.
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Goldman J, Gordon M
Leuk Lymphoma. 2006 Jan ; 47(1): 1-7
It is generally accepted that allogeneic stem cell transplantation can ‘cure’ chronic myelogenous leukemia (CML), although occasional patients relapse more than 10 years after the transplant procedure. Such cures presumably result from the combined effects of leukemia stem cells (LSCs) of the conditioning regimen and the graft-vs.-leukemia (GvL) effect mediated by donor-derived T lymphocytes. The advent of imatinib has revolutionized the management of patients with CML, but much evidence suggests that it does not eradicate all LSCs, which theoretically remain a potential source of relapse to chronic phase or advanced phase disease. Moreover, sub-clones of Philadelphia-positive cells bearing mutations that code for amino-acid substitutions in the Bcr-Abl kinase domain can be identified in patients receiving treatment with imatinib and are associated with varying degrees of resistance to this agent. In the present review, we postulate that LSCs, similar to their normal counterparts, may alternate between cycling and quiescent modes. In the cycling mode, they may express Bcr-Abl protein and be susceptible to the acquisition of additional mutations, whereas, in the quiescent mode, they may express little or no Bcr-Abl oncoprotein, cannot acquire additional mutations and are unaffected by imatinib. Thus, a patient who starts treatment early in the natural history of CML, and who responds to imatinib clinically, may not have had the opportunity to acquire additional mutations in LSCs. In this case, the persistence long-term of quiescent ‘non-mutated’ LSCs despite imatinib treatment might be consistent with freedom from relapse to chronic or advanced phase disease, provided that they remain vulnerable to imatinib when they are recruited into cycle. Conversely, when imatinib resistant Philadelphia-positive sub-clones predominate, this is likely to be due to the recruitment to hematopoiesis of quiescent stem cells that had been in cycle before administration of imatinib and that had acquired additional mutations; in such cases, the best approach to eradication of residual LSCs might be to target expressed proteins thought to be targets for the GvL effect.
Posted by rob on December 14, 2005 under Uncategorized | Be the First to Comment
SAN DIEGO, Dec. 13 /PRNewswire/ — SGX Pharmaceuticals announced that it will present data today at the American Society of Hematology’s 47th Annual Meeting and Exposition showing that compounds discovered by applying its FAST(TM) lead discovery platform potently inhibit wild-type and Gleevec-resistant BCR-ABL, including the most clinically challenging mutation T315I.
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The clinical success of Gleevec has demonstrated that BCR-ABL kinase inhibitors can provide effective treatment of Chronic Myelogenous Leukemia (CML). However, some patients develop resistance to Gleevec therapy, which occurs due to point mutations in the BCR-ABL kinase and there is currently no approved pharmaceutical treatment for such Gleevec-resistant CML. Although effective against many of the other clinically relevant mutants, second-generation BCR-ABL inhibitors currently in clinical studies have not been shown to inhibit T315I, which represents about 20 percent of clinically observed mutations and is one of the most common causes of resistance to treatment with Gleevec.
During an oral presentation in the session entitled “Chronic Myelogenous Leukemia: Molecular Mechanisms of Disease and Resistance” taking place today at 9:45 a.m., Stephen K. Burley, M.D., D.Phil., SGX Pharmaceutical’s Chief Scientific Officer and Senior Vice President, Research, will present in vitro and in vivo data showing that compounds in SGX’s most advanced lead series potently inhibit proliferation of K562 cells and Ba/F3 cells with wild-type BCR-ABL and most clinically-relevant mutations, including T315I.
SGX expects to file an IND in late 2006 to permit clinical development of a compound from its lead series of BCR-ABL kinase inhibitors for treatment of drug-resistant CML.
About SGX Pharmaceuticals
SGX Pharmaceuticals (SGX) is a biotechnology company focused on the discovery, development and commercialization of innovative cancer therapeutics. More information can be found at www.sgxpharma.com .
SGX Pharmaceuticals Presenting Data at American Society of Hematology Annual Meeting on Inhibitors of Wild-Type and Gleevec(R)-Resistant BCR-ABL Kinase: Financial News – Yahoo! Finance
