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BCR-ABL signaling: A new STATus in CML
Nature Chemical Biology 8, 228 (2012).
doi:10.1038/nchembio.900
Author: Doriano Fabbro
A combination of genetic and pharmacological approaches using mouse leukemia models show that STAT5 phosphorylation is one of the major drivers of the proliferation of Philadelphia chromosome–positive (BCR-ABL-positive or Ph+) chronic myeloid leukemia. Once BCR-ABL expression has been established, JAK2 is required only for lymphoid cell transformation, not for the maintenance of the lymphoid or myeloid leukemia. (Source: Nature Chemical Biology)
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Secondary hyperparathyroidism but stable bone mineral density in patients with chronic myeloid leukemia treated with imatinib
(Source: American Journal of Hematology)
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Genetic Mechanisms of Chronic Myeloid Leukemia Blastic Transformation
Abstract The BCR-ABL1 oncogenic tyrosine kinase can transform pluripotent hematopoietic stem cells and initiate chronic myeloid leukemia
in chronic phase (CML-CP), a myeloproliferative disorder characterized by excessive accumulation of mature myeloid cells.
Patients in CML-CP usually respond to treatment with ABL1 tyrosine kinase inhibitors (TKIs) such as imatinib, though some
patients who respond initially may become resistant later. CML-CP leukemia stem cells (LSCs) are intrinsically insensitive
to TKIs and thus survive in the long term. These LSCs or their progeny may at some stage acquire additional genetic changes
that cause the leukemia to transform further, from CML-CP to a more advanced phase, which has been subclassified as either
accelerated phase (CML-AP) or bl...
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Novel four-way Ph translocation t(9;22;7;1)(q34;q11;q22;p13) in a chronic myeloid leukemia patient receiving tyrosine kinase inhibitor therapy.
We describe a case of a chronic myeloid leukemia (CML) patient with a complex four-way t(9;22;7,1) translocation who received multiple tyrosine kinase inhibitor therapy. As evaluation of prognostic features in a limited number of patients with four-way Philadelphia rearrangements at present yields controversial results, our case may add further information on the prognostic impact of such abnormalities in CML patients receiving tyrosine kinase inhibitor therapy, and may help delineate a sub-group of patients requiring different therapeutic approaches.
PMID: 22322321 [PubMed - as supplied by publisher] (Source: International Journal of Hematology)
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Hairy Cell Leukemia Variant in a Patient With Chronic Myeloid Leukemia Receiving Nilotinib: Sequential or Coincidental? [DIAGNOSIS IN ONCOLOGY]
(Source: Journal of Clinical Oncology)
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Chronic myeloid leukemia stem cells are not dependent on Bcr-Abl kinase activity for their survival
Recent evidence suggests chronic myeloid leukemia (CML) stem cells are insensitive to kinase inhibitors and responsible for minimal residual disease in treated patients. We investigated whether CML stem cells, in a transgenic mouse model of CML-like disease or derived from patients, are dependent on Bcr-Abl. In the transgenic model, after retransplantation, donor-derived CML stem cells in which Bcr-Abl expression had been induced and subsequently shut off were able to persist in vivo and reinitiate leukemia in secondary recipients on Bcr-Abl reexpression. Bcr-Abl knockdown in human CD34+ CML cells cultured for 12 days in physiologic growth factors achieved partial inhibition of Bcr-Abl and downstream targets p-CrkL and p-STAT5, inhibition of proliferation and colony forming cells, but no r...
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Plasma exposure of imatinib and its correlation with clinical response in the Tyrosine Kinase Inhibitor Optimization and Selectivity Trial.
Conclusions. Imatinib Cmin levels were relatively stable over time and proportional to the dose administered. Patients with an imatinib Cmin above 1165 ng/mL on day 29 achieved major molecular response faster and had higher major molecular response and complete cytogenetic response rates at 12 months. There appeared to be an association between imatinib Cmin and the frequency of some adverse events. This trial was registered at http://www.clinicaltrials.gov as NCT00124748.
PMID: 22315495 [PubMed - as supplied by publisher] (Source: Haematologica)
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Dasatinib or imatinib in newly diagnosed chronic-phase chronic myeloid leukemia: 2-year follow-up from a randomized phase 3 trial (DASISION)
This study was registered at ClinicalTrials.gov: NCT00481247. (Source: Blood)
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Chronic Myelomonocytic Leukemia and Atypical Chronic Myeloid Leukemia: Novel Pathogenetic Lesions
Chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML) are distinct, yet related, entities of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) characterized by morphologic dysplasia with accumulation of monocytes or neutrophils, respectively. Our understanding of the molecular pathogenesis of CMML and aCML has advanced, mainly due to the application of novel technologies such as array-based karyotyping and next-generation sequencing. In addition to previously known recurrent aberrations, somatic uniparental disomy affecting chromosomes 3, 4, 7, and 11 frequently occurs in CMML. Novel somatic mutations of genes, including those associated with proliferation signaling (CBL, RAS, RUNX1, JAK2 (V617F)) and with modification of epigenetic status (TET2, ASXL1, U...
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Chronic Myeloid Leukemia: Clinical Impact of BCR-ABL1 Mutations and Other Lesions Associated With Disease Progression
The introduction of the tyrosine kinase inhibitors (TKIs) imatinib, dasatinib, and nilotinib has dramatically improved the treatment of chronic myeloid leukemia (CML). However, a minority of CML patients in chronic phase (CP) and a substantial proportion of patients in advanced phase are either initially refractory to TKIs or eventually develop resistance. Rates of resistance and relapse directly correlate with disease progression. The most frequently identified mechanism of acquired TKI resistance is BCR-ABL1 kinase domain (KD) mutations that impair TKI binding by disrupting the drug contact sites or causing conformational changes that make the contact sites inaccessible. The underlying mechanisms of disease progression are heterogeneous and only poorly understood. So far the most frequen...
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Donor Atorvastatin Calcium in Preventing Severe Acute Graft-Versus-Host Disease in Patients Undergoing Donor Peripheral Blood Stem Cell Transplant
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BCR-ABL kinase domain mutations in tyrosine kinase inhibitors-naïve and -exposed Southeast Asian chronic myeloid leukemia patients.
In conclusion, several known and novel BCR-ABL KD mutations were discovered in the TKI-naïve and -exposed Southeast Asian CML patients, supporting the concept that naturally occurring KD mutations were present in leukemic cells prior to drug exposure. T315I resistant mutation was completely undetectable in this naïve Southeast Asian cohort; its incidence, however, increases with drug exposure.
PMID: 22314255 [PubMed - as supplied by publisher] (Source: Experimental and Molecular Pathology)
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Estimations of the increasing prevalence and plateau prevalence of chronic myeloid leukemia in the era of tyrosine kinase inhibitor therapy
CONCLUSIONS:The current results indicated that the prevalence of CML will continue to increase to reach a near plateau prevalence 35 times the annual incidence. These estimates should be considered in health care policies and in the design of future studies in CML. Cancer 2012. © 2012 American Cancer Society. (Source: Cancer)
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Pfizer Announces FDA Acceptance Of New Drug Application For Bosutinib For Patients With Previously Treated Ph+ Chronic Myeloid Leukemia
NEW YORK--(BUSINESS WIRE)--Jan 27, 2012 - Pfizer Inc. announced
today that the U.S. Food and Drug Administration (FDA) has accepted
its New Drug Application (NDA) for standard review of bosutinib as
a treatment option for adult patients with... (Source: Drugs.com - New Drug Applications)
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BCR-ABL uncouples canonical JAK2-STAT5 signaling in chronic myeloid leukemia
Authors: Oliver Hantschel, Wolfgang Warsch, Eva Eckelhart, Ines Kaupe, Florian Grebien, Kay-Uwe Wagner, Giulio Superti-Furga & Veronika Sexl (Source: Nature Chemical Biology)
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Combining Nilotinib and Imatinib Improves the Outcome of Imatinib-Resistant Blast Phase CML.
Authors: Zhu GR, Ji O, Ji JM, Zhang YC, Wu Y, Yu H, Jiang PJ, Shen Q
Abstract
Imatinib resistance is an important hurdle in the treatment of chronic myeloid leukemia (CML), and CML patients with this drug resistance are often given a dismal prognosis. In this case report, an imatinib-refractory blast phase CML patient was treated with a combination of imatinib and nilotinib. A complete hematologic response was achieved within 3 months, the drug combination was well tolerated, and there was a relatively long bone-marrow complete remission. These results suggest that combining imatinib and nilotinib treatment may improve the outcome of imatinib-resistant CML patients in the blast phase. We hypothesize regarding the possible mechanism for the effectiveness of the drug combination by r...
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Splenic infarction in a child revealing chronic myeloid leukemia
Abstract A 7-year-old girl was admitted with a severe abdominal pain. Abdominal ultrasound and CT revealed a large splenic infarction,
leading to the diagnosis of chronic myeloid leukemia.
Content Type Journal ArticleCategory Images in PediatricsPages 1-2DOI 10.1007/s00431-012-1675-yAuthors
David Drummond, Department of Pediatric Hematology and Oncology, Hôpital Armand Trousseau, Assistance Publique Hôpitaux de Paris (APHP), Université Pierre et Marie Curie (Paris 6), 26, avenue Arnold Netter, 75012 Paris, FranceMarion Lenoir, Department of Radiology, Hôpital Armand Trousseau, Assistance Publique Hôpitaux de Paris (APHP), Université Pierre et Marie Curie (Paris 6), 26, avenue Arnold Netter, 75012 Paris, FranceArnaud Y. Petit, Department of Pediatric Hematology and ...
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Dasatinib: From Treatment of Imatinib-Resistant or -Intolerant Patients With Chronic Myeloid Leukemia to Treatment of Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia.
CONCLUSIONS: Dasatinib was an effective treatment with the potential to improve long-term outcomes for patients with newly diagnosed CML-CP.
PMID: 22285209 [PubMed - as supplied by publisher] (Source: Clinical Therapeutics)
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Quality Of Life Issues For Patients With Chronic Myeloid Leukemia
Although significant progress has been made in treating chronic myeloid leukemia, the disease cannot yet be eliminated in all patients, and that challenge must be addressed, states a commentary in CMAJ (Canadian Medical Association Journal).). Likening the journey to find a cure for chronic myeloid leukemia as a marathon, cancer expert Dr. Jorge Cortes, University of Texas, MD Anderson Cancer Center, Houston, Texas, writes, "The past half century has been an extraordinary run that has us on an excellent pace to not only complete the race to a cure, but to do so in record time... (Source: Health News from Medical News Today)
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Chronic myeloid leukemia: The race is yet to be won.
Authors: Cortes J
PMID: 22271914 [PubMed - as supplied by publisher] (Source: cmaj)
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The race against chronic myeloid leukemia not yet won
(Canadian Medical Association Journal) Although significant progress has been made in treating chronic myeloid leukemia, the disease cannot yet be eliminated in all patients, and that challenge must be addressed, states a commentary in CMAJ. (Source: EurekAlert! - Social and Behavioral Science)
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Clinical cardiac safety profile of nilotinib.
Conclusions. Whereas new electrocardiographic abnormalities were recorded in twenty percent of all patients and some of them developed severe or even life-threatening coronary artery disease, QT prolongation, changes in left ventricular ejection fraction, and clinical cardiac adverse events were uncommon in patients treated with nilotinib.
PMID: 22271904 [PubMed - as supplied by publisher] (Source: Haematologica)
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Analysis of outcomes in adolescents and young adults with chronic myelogenous leukemia treated with upfront tyrosine kinase inhibitor therapy.
Conclusions: The unfavorable trend in outcome for adolescent and young adult with chronic myeloid leukemia is unexpected. Additional research in this population is required to better define outcomes, understand the cause of this difference, and to help make better treatment recommendations.
PMID: 22271898 [PubMed - as supplied by publisher] (Source: Haematologica)
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Analysis of non-HLA genomic risk factors in HLA-matched unrelated donor hematopoietic cell transplantation for chronic myeloid leukemia.
Conclusions. We did not confirm that non-Human Leukocyte Antigen polymorphisms were associated with outcomes in myeloablative unrelated donor hematopoietic cell transplantation for Chronic Myeloid Leukemia, possibly due to the strong association between clinical variables and outcome that masked more subtle genetic effects.
PMID: 22271889 [PubMed - as supplied by publisher] (Source: Haematologica)
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The significance of major and stable molecular responses in chronic myeloid leukemia in the tyrosine kinase inhibitor era
Tyrosine kinase inhibitors have changed the management and outcomes of chronic myeloid leukemia patients. Quantitative polymerase chain reaction is used to monitor molecular responses to tyrosine kinase inhibitors. Molecular monitoring represents the most sensitive tool to judge chronic myeloid leukemia disease course and allows early detection of relapse. Evidence of achieving molecular response is important for several reasons: 1. early molecular response is associated with major molecular response rates at 18-24 months; 2. patients achieving major molecular response are less likely to lose their complete cytogenetic response; 3. a durable, stable major molecular response is associated with increased progression-free survival. However, standardization of molecular techniques is still cha...
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Imatinib resistance: a review of alternative inhibitors in chronic myeloid leukemia
This article, a review of possible therapies used to overcome imatinib resistance, investigates the current position by searching the PubMed electronic database using the following keywords: imatinib, dasatinib, nilotinib, aurora kinase, SRC kinase, mutation, treatment, drugs and resistance. New tyrosine kinase inhibitors include BCR-ABL kinase selective inhibitors, dual ABL/SRC kinase inhibitors and aurora kinase inhibitors. Awareness of the spectrum of new drugs against mutations, in particular the T315I mutation, makes it possible to properly select the best therapy for each patient (Source: Revista Brasileira de Hematologia e Hemoterapia)
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AWMSG issues Final Appraisal Recommendation on dasatinib (Sprycel®)
Source: All Wales Medicines Strategy Group (AWMSG)
Area: Evidence > Drug Specific Reviews
In its Final Appraisal Recommendation, the All Wales Medicines Strategy Group (AWMSG) does not support the use of dasatinib (Sprycel®) within NHS Wales for the treatment of adult patients with newly diagnosed Philadelphia chromosome positive (Ph+) chronic myelogenous leukaemia in the chronic phase. The group considered that the case for cost effectiveness had not been proven. (Source: NeLM - Drug Specific Reviews)
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Pharmacokinetics of nilotinib in imatinib‐resistant/intolerant chronic myeloid leukemia patients on hemodialysis for chronic renal failure
(Source: American Journal of Hematology)
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ICB3E induces iNOS expression by ROS-dependent JNK and ERK activation for apoptosis of leukemic cells
Abstract The role of c-Jun N terminal Kinase (JNK) has been well documented in various cellular stresses where it leads to cell death. Similarly, extracellular
signal-regulated kinase (ERK) which was identified as a signalling molecule for survival pathway has been shown recently to
be involved in apoptosis also. Recently we reported that ICB3E, a synthetic analogue of Piper betle leaf-derived apoptosis-inducing agent hydroxychavicol (HCH), possesses anti-chronic myeloid leukemia (CML) acitivity in vitro
and in vivo without insight on mechanism of action. Here we report that ICB3E is three to four times more potent than HCH
in inducing apoptosis of leukemic cells without having appreciable effects on normal human peripheral blood mononuclear cells,
mouse fibroblast cell lin...
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Not Only Response but Early Response to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia [EDITORIALS]
(Source: Journal of Clinical Oncology)
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Allopurinol-induced palisaded neutrophilic and granulomatous dermatitis.
We describe a 64-year-old man with past chronic myeloid leukemia. Palisading neutrophilic granulomatous dermatitis of the hands was diagnosed and related to recent allopurinol intake. Allopurinol is known to rarely cause granulomatous reactions, but this appears to be the first case of palisading neutrophilic granulomatous dermatitis induction. Possible mechanisms include immune complex deposition, an immune response directed against the metabolites of allopurinol, or allopurinol hypersensitivity exclusively localized to the skin.
PMID: 22250812 [PubMed - as supplied by publisher] (Source: Cutaneous and Ocular Toxicology)
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Assessment of BCR-ABL1 Transcript Levels at 3 Months Is the Only Requirement for Predicting Outcome for Patients With Chronic Myeloid Leukemia Treated With Tyrosine Kinase Inhibitors [Rapid Communication]
Conclusion
A single measurement of BCR-ABL1 transcripts performed at 3 months is the best way to identify patients destined to fare poorly, thereby allowing early clinical intervention. (Source: Journal of Clinical Oncology)
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Absence of DNMT3A gene mutation in chronic myeloid leukemia patients in blast crisis
(Source: European Journal of Haematology)
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Continuing Good News for Chronic Myeloid Leukemia Patients
The results of the 2-year follow-up of the dasatinib DASISION phase III trial show the continued superiority of the drug compared to imatinib. The results provide further support for treatment of first-line chronic phase chronic myeloid leukemia patients that harbor the Philadelphia chromosome. (Source: Cancer Network)
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Spotlight on Dasatinib in Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
(Source: BioDrugs)
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Low BCR-ABL expression levels in hematopoietic precursor cells enable persistence of chronic myeloid leukemia under imatinib
BCR-ABL overexpression and stem cell quiescence supposedly contribute to the failure of imatinib mesylate (IM) to eradicate chronic myeloid leukemia (CML). However, BCR-ABL expression levels of persisting precursors and the impact of long-term IM therapy on the clearance of CML from primitive and mature bone marrow compartments are unclear. Here, we have shown that the number of BCR-ABL–positive precursors decreases significantly in all bone marrow compartments during major molecular remission (MMR). More importantly, we were able to demonstrate substantially lower BCR-ABL expression levels in persisting MMR colony-forming units (CFUs) compared with CML CFUs from diagnosis. Critically, lower BCR-ABL levels may indeed cause IM insensitivity, because primary murine bone marrow cells en...
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International Reporting Scale of BCR-ABL1 Fusion Transcript in Chronic Myeloid Leukemia: First Report from India.
In this report, we explain the process and steps involved in obtaining a valid lab-specific conversion factor for expressing BCR-ABL1 transcript levels in the IS.
PMID: 22249155 [PubMed - as supplied by publisher] (Source: Acta Haematologica)
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Prolonged Survival with Imatinib Mesylate Combined with Chemotherapy and Allogeneic Stem Cell Transplantation in de novo Ph+ Acute Myeloid Leukemia.
Conclusions: Our cases indicate that IM combined with daunorubicin-based chemotherapy followed by allo-HSCT and IM maintenance treatment is associated with a favorable outcome for de novo Ph+ AML, especially when IM is used in an early phase of AML.
PMID: 22248505 [PubMed - as supplied by publisher] (Source: Acta Haematologica)
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Four-channel asymmetric Real-Time PCR hybridization probe assay: A rapid pre-screening method for critical BCR-ABL kinase domain mutations.
CONCLUSIONS: This new methodology detects in a few steps the presence of critical mutations associated to Imatinib resistance.
PMID: 22266405 [PubMed - as supplied by publisher] (Source: Clinical Biochemistry)
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Imatinib trough plasma levels do not correlate with the response to therapy in patients with chronic myeloid leukemia in routine clinical setting
Abstract Association of trough imatinib plasma levels (IPL) with cytogenetic or molecular response to treatment in patients with chronic
myeloid leukemia (CML) was repeatedly reported. We analyzed their value in the routine clinical setting in 131 patients with
chronic phase CML in whom imatinib was applied as first- or second-line treatment. A total of 1,118 measurements were obtained
by ultra-performance liquid chromatography–tandem mass spectrometry assay in patients treated with daily dose of imatinib
ranging from 100 to 800 mg. Samples were obtained from 1 to 96 h after drug ingestion. High inter (36%) and intraindividual
variability (9–33%) of IPL was observed. For analysis of correlation of IPL with treatment response, two sets of samples were
selected...
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Anti-leukemic effects of gallic acid on human leukemia K562 cells: Downregulation of COX-2, inhibition of BCR/ABL kinase and NF-κB inactivation.
In conclusion, GA induced apoptosis in K562 cells involves death receptor and mitochondrial-mediated pathways by inhibiting BCR/ABL kinase, NF-κB activity and COX-2.
PMID: 22245431 [PubMed - as supplied by publisher] (Source: Toxicology in Vitro)
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Distinct graft-versus-leukemic stem cell effects of early or delayed donor leukocyte infusions in a mouse chronic myeloid leukemia model
Among hematologic neoplasms, chronic myeloid leukemia (CML) is exquisitely sensitive to graft-versus-leukemia (GVL) because patients relapsing after allogeneic hematopoietic stem-cell transplantation (alloHSCT) can be cured by donor leukocyte infusion (DLI); however, the cellular mechanisms and strategies to separate GVL from GVHD are unclear. We used a BCR-ABL1 transduction/transplantation mouse model to study the mechanisms of DLI in MHC-matched, minor histocompatibility antigen–mismatched allogeneic chimeras with CML-like leukemia, in which DLI can be administered at the time of transplantation (early) or after recovery of hematopoiesis (delayed). After early DLI, CML-like leukemia cannot be transferred into immunocompetent secondary recipients as soon as 4 days after primary tran...
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Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate
ConclusionSkin changes are the most common non‐hematologic side effects to IM treatment and are usually dose dependent. In particular, patients with IM therapy reported a lightening and depigmentation of the skin, that may alter the skin protection against ultraviolet exposure, with a possible subsequent intolerance to sun exposure, as reported in our patient, and higher risk of skin cancer. They are frequently self‐limited or easily managed; nevertheless, in some cases, the therapy needs to be discontinued or may only be continued with concomitant oral steroid. (Source: Photodermatology, Photoimmunology and Photomedicine)
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Mucosal Pigmentation Caused by Imatinib: Report of Three Cases
Abstract Imatinib mesylate (STI-571, Gleevec®), a tyrosine kinase inhibitor, is a first-line medication for treating chronic myeloid leukemia (CML). Clinical studies revealed
very good hematological responses without significant side effects. However, imatinib may lead to mucosal pigmentation. Three
patients, two males aged 64 and 53 and one female aged 29 presented with a painless, diffuse, grey-blue pigmentation of the
mucosa of the hard palate. Both male patients had a history of CML and had been on imatinib for 4 and 10 years, respectively.
The female patient had been on imatinib for 4 years for pelvic fibromatosis. Histopathologically, deposition of fine, dark-brown,
spherical granules was noted within the connective tissue. There was no inflammation or hemo...
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A new dic(7;12)(p12.21;p12.2) and i(12)(q10) during the lymphoid blast crisis of patient with Ph+ chronic myeloid leukemia
Abstract Chronic myelogenous leukemia (CML) is a common myeloproliferative disease that is characterized by the clonal expansion of
marrow stem cells, and is associated with the Philadelphia chromosome. As the disease progresses, additional chromosome abnormalities may arise. The prognostic impact of secondary
chromosomal abnormalities in CML is complex, heterogeneous, and sometimes related to previous treatment. Here, we describe
a CML patient in lymphoid blast crisis associated with a new chromosomal abnormality identified, dic(7;12)(p12.21;p12.2) and
i(12)(q10) using classical cytogenetics and spectral karyotype analysis. To the best of our knowledge, this is the first report
of t(7;12)(p11.1;q11.1) and i(12)(q10) in a CML patient with lymphoid evolution.
Content Ty...
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Population pharmacokinetic and exposure-response analysis of nilotinib in patients with newly diagnosed Ph+ chronic myeloid leukemia in chronic phase
Conclusions There is a less than proportional dose-exposure relationship between nilotinib 300 mg and 400 mg twice-daily doses. Blood
level testing is unlikely to play an important role in the general management of patients with newly diagnosed CML treated
with nilotinib.
Content Type Journal ArticleCategory Pharmacokinetics and DispositionPages 1-11DOI 10.1007/s00228-011-1200-7Authors
Richard A. Larson, University of Chicago, Chicago, IL, USAOphelia Q. P. Yin, Novartis Pharmaceuticals Corporation, Florham Park, NJ, USAAndreas Hochhaus, Universitätsklinikum Jena, Jena, GermanyGiuseppe Saglio, University of Turin, Orbassano, ItalyRichard E. Clark, Royal Liverpool University Hospital, Liverpool, UKHirohisa Nakamae, Osaka City University, Osaka, JapanNeil J....
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Chronic phase chronic myeloid leukemia patients with low OCT-1 activityrandomised to high-dose imatinib achieve better responses, and lower failure rates, than those randomized to standard-dose.
Conclusions. High dose imatinib leads to superior molecular responses in patients with low OCT-1 activity. In this group trough imatinib levels may define a group with inferior outcomes. For high OCT-1 activity patients higher imatinib dosing or monitoring of imatinib trough levels were not found to be of significant clinical value. Hence OCT-1 activity determined prior to the start of therapy in newly diagnosed CML patients provides a valuable prognostic tool to determine the optimal up-front dose of imatinib in newly diagnosed chronic phase chronic myeloid leukaemia patients.
PMID: 22207690 [PubMed - as supplied by publisher] (Source: Haematologica)
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Exosomes released by K562 chronic myeloid leukemia cells promote angiogenesis in a src-dependent fashion
Abstract Exosomes, microvesicles of endocytic origin released by normal and tumor cells, play an important role in cell-to-cell communication.
Angiogenesis has been shown to regulate progression of chronic myeloid leukemia (CML). The mechanism through which this happens
has not been elucidated. We isolated and characterized exosomes from K562 CML cells and evaluated their effects on human umbilical
endothelial cells (HUVECs). Fluorescent-labeled exosomes were internalized by HUVECs during tubular differentiation on Matrigel.
Exosome localization was perinuclear early in differentiation, moving peripherally in cells undergoing elongation and connection.
Exosomes move within and between nanotubular structures connecting the remodeling endothelial cells. They stimulated angiot...
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Imatinib in chronic myeloid leukemia elderly patients.
Authors: Gugliotta G, Castagnetti F, Palandri F, Baccarani M, Rosti G
Abstract
Second generation tyrosine kinase inhibitors (dasatinib and nilotinib) as front-line therapy showed higher response rates and lower toxicities compared to IM; probably these results will be confirmed also in elderly patients. Importantly, extra-hematologic toxicities are distinct between IM, dasatinib and nilotinib, allowing the selection of the more appropriate drug in relation to the presence of co-morbidities. Although data on dasatinib and nilotinib in elderly patients are still few and the follow-up is still short, these second generation tyrosine kinase inhibitors will probably further improve the outcome of CML elderly patients.
PMID: 22203437 [PubMed - as supplied by publisher] (Source: Aging...
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Two New Winners for CML?Two New Winners for CML?
The drugs keep coming -- and the results remain impressive -- for treatment of chronic myeloid leukemia. Medscape Hematology-Oncology (Source: Medscape Today Headlines)
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