ABL kinase inhibitory and antiproliferative activity of novel picolinamide based benzothiazoles.

Posted by rob on April 18, 2015 under Uncategorized | Comments are off for this article

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ABL kinase inhibitory and antiproliferative activity of novel picolinamide based benzothiazoles.

Bioorg Med Chem Lett. 2015 Mar 31;

Authors: El-Damasy AK, Cho NC, Kang SB, Pae AN, Keum G

Abstract

A series of novel picolinamide based benzothiazoles (17 final compounds), targeting both wild-type and the most resistant T315I mutant of Bcr-Abl kinase, has been designed and synthesized. Moreover, a selected array (8 compounds) was evaluated for its antiproliferative activity over a panel of 60 cancer cell lines. Compound 5l was the most potent derivative against both native and T315I mutant ABL with IC50 values of 18.2 and 39.9nM, respectively, and showed highly selective inhibitory activity (89.8%) towards the Bcr-Abl dependent leukemia cell (K-562) at 10?M concentration. Significance of C6-oxypicolinamide moiety and SAR study for the C2 aliphatic side chain of benzothiazole are discussed in detail.

PMID: 25881828 [PubMed - as supplied by publisher]

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[Difference in measurements of erythrocyte sedimentation rate obtained using two devices of the same model in a patient with marked leukocytosis].

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[Difference in measurements of erythrocyte sedimentation rate obtained using two devices of the same model in a patient with marked leukocytosis].

Rinsho Byori. 2014 Jul;62(7):664-7

Authors: Nojiri T, Masuda A, Ohkawa R, Koido K, Shimosaka H, Okubo S, Yokota H, Kurano M, Nannya Y, Ikeda H, Kurokawa M, Yatomi Y

Abstract

The erythrocyte sedimentation rate (ESR) has been used as an index for inflammatory conditions, such as infectious diseases, autoimmune diseases, and malignancies. The ESR values of a 37-year-old male with marked leukocytosis due to chronic myeloid leukemia showed remarkable differences between two devices of the same model (Ves-Matic 30, DIESSE Diagnostica Senese). From the appearance of the tested tube after the ESR measurement, the values obtained using one device might have been falsely low, whereas the values obtained using the other device were likely to have been accurate. The difference of the ESR values between the two devices might have occurred by the false detection of transmitted light during the transition from the erythrocyte layer to the leukocyte layer. These findings suggest that in cases with marked leukocytosis the accuracy of ESR should be confirmed with the appearance of the test tube.

PMID: 25669035 [PubMed - indexed for MEDLINE]

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Single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) and risk of chronic myeloid leukemia.

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Single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) and risk of chronic myeloid leukemia.

Tumour Biol. 2014 Nov;35(11):10969-75

Authors: Yaya K, Hind D, Meryem Q, Asma Q, Said B, Sellama N

Abstract

Multidrug resistance gene 1 (MDR1) is known for its involvement in the detoxification through the active transport of toxic compounds from diverse origins outside the cells. These compounds could cause injury to cell DNA, which might lead in cancer like chronic myeloid leukemia (CML). Individual inherited genetic differences related to polymorphism in detoxification enzymes could be an important factor not only in carcinogen metabolism but also in susceptibility of cancer. The present study aimed to investigate the association of three single nucleotide polymorphisms (SNPs) of the MDR1 gene in the susceptibility of CML. We successively have determined the genotype profiles of 1236 C>T (exon 12); 2677 G>T (exon 21), and 3435 C>T (exon 26) SNPs by PCR-RFLP in 89 patients and 99 unrelated healthy controls. Logistic regression was used to assess the effect of each SNP on the development of CML. Interestingly, in exon 12, the 1236 TT was significantly associated with the susceptibility of CML when compared to the wild type 1236 CC (OR 2.7; 95% CI 1-7.32, p = 0.041). Additionally, the recessive model 1236 TT vs. 1236 CC/CT showed a risk of 3.3 fold (p = 0.011) with CML. In exon 26, the 3435 CT genotype was associated with a reduced risk of CML (OR 0.5; 95% CI 0.3-1, p = 0.042). In exon 21, the 2677 GT genotype seems to have a protective effect (OR 0.6; 95% CI 0.32-1.1, p = 0.074). Diplolotypes analysis has demonstrated no effect in susceptibility of CML, but 1236 CT/3435 CC and 1236 CC/2677 GT were associated with a protective effect. The haplotypes analysis showed no particular trend (global association p = 0.33). Our findings demonstrate that 1236 TT in exon 12 might contribute in the susceptibility of CML, while the 3435 CT in exon 26 as well as 1236 CT/3435 CC and 1236 CC/2677 GT combinations might be protective factors.

PMID: 25087925 [PubMed - indexed for MEDLINE]

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Risk and impact of tuberculosis in patients with chronic myeloid leukemia: a nationwide population-based study in Taiwan.

Posted by rob on April 17, 2015 under Uncategorized | Comments are off for this article

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Risk and impact of tuberculosis in patients with chronic myeloid leukemia: a nationwide population-based study in Taiwan.

Int J Cancer. 2015 Apr 15;136(8):1881-7

Authors: Liu CJ, Hong YC, Teng CJ, Hung MH, Hu YW, Ku FC, Chen YT, Chien SH, Yeh CM, Chen TJ, Chiou TJ, Gau JP, Tzeng CH

Abstract

The relationship between chronic myeloid leukemia (CML) and tuberculosis (TB) has not been determined. We conducted a national survey including 1,082 CML patients identified from the Taiwan National Health Insurance database covering a period between 1998 and 2011; the matched non-exposed cohort included 10,820 subjects without CML that were matched for age, sex and comorbidities. The impact of TB was measured by the overall mortality, and the risk factors were identified by a multivariate Cox proportional hazards model. We found the risk of TB was higher in the CML cohort, with an adjusted hazard ratio (aHR) of 3.76 (p?=?0.001) for both pulmonary (aHR 3.23, p?<?0.001) and extrapulmonary (aHR 9.77, p?=?0.001) TB. Specific risk factors were: aged???60 (aHR 3.24, p?=?0.022), being male (aHR 13.49, p?=?0.012), receiving stem cell transplantation (aHR 10.50, p?=?0.001) and interferon-? therapy (aHR 3.34, p?=?0.011). CML patients with TB had a higher mortality rate than those without (aHR 2.04, p?=?0.043). We conclude that the incidence of TB is significantly higher in CML patients of male sex, aged???60, having received either stem cell transplantation or interferon-? treatment. Careful screening strategies for TB should be considered for CML patients with high risk of the infection.

PMID: 25208807 [PubMed - indexed for MEDLINE]

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Anti-leukemic potency of piggyBac-mediated CD19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.

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Anti-leukemic potency of piggyBac-mediated CD19-specific T cells against refractory Philadelphia chromosome-positive acute lymphoblastic leukemia.

Cytotherapy. 2014 Sep;16(9):1257-69

Authors: Saito S, Nakazawa Y, Sueki A, Matsuda K, Tanaka M, Yanagisawa R, Maeda Y, Sato Y, Okabe S, Inukai T, Sugita K, Wilson MH, Rooney CM, Koike K

Abstract

BACKGROUND AIMS: To develop a treatment option for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) resistant to tyrosine kinase inhibitors (TKIs), we evaluated the anti-leukemic activity of T cells non-virally engineered to express a CD19-specific chimeric antigen receptor (CAR).

METHODS: A CD19.CAR gene was delivered into mononuclear cells from 10 mL of blood of healthy donors through the use of piggyBac-transposons and the 4-D Nucleofector System. Nucleofected cells were stimulated with CD3/CD28 antibodies, magnetically selected for the CD19.CAR, and cultured in interleukin-15-containing serum-free medium with autologous feeder cells for 21 days. To evaluate their cytotoxic potency, we co-cultured CAR T cells with seven Ph(+)ALL cell lines including three TKI-resistant (T315I-mutated) lines at an effector-to-target ratio of 1:5 or lower without cytokines.

RESULTS: We obtained ?1.3 × 10(8) CAR T cells (CD4(+), 25.4%; CD8(+), 71.3%), co-expressing CD45RA and CCR7 up to ?80%. After 7-day co-culture, CAR T cells eradicated all tumor cells at the 1:5 and 1:10 ratios and substantially reduced tumor cell numbers at the 1:50 ratio. Kinetic analysis revealed up to 37-fold proliferation of CAR T cells during a 20-day culture period in the presence of tumor cells. On exposure to tumor cells, CAR T cells transiently and reproducibly upregulated the expression of transgene as well as tumor necrosis factor-related apoptosis-inducing ligand and interleukin-2.

CONCLUSIONS: We generated a clinically relevant number of CAR T cells from 10 mL of blood through the use of piggyBac-transposons, a 4D-Nulcleofector, and serum/xeno/tumor cell/virus-free culture system. CAR T cells exhibited marked cytotoxicity against Ph(+)ALL regardless of T315I mutation. PiggyBac-mediated CD19-specific T-cell therapy may provide an effective, inexpensive and safe option for drug-resistant Ph(+)ALL.

PMID: 25108652 [PubMed - indexed for MEDLINE]

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Allogeneic stem cell transplantation for Philadelphia chromosome-positive acute myeloid leukemia.

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Allogeneic stem cell transplantation for Philadelphia chromosome-positive acute myeloid leukemia.

J Natl Compr Canc Netw. 2014 Jul;12(7):963-8

Authors: Bhatt VR, Akhtari M, Bociek RG, Sanmann JN, Yuan J, Dave BJ, Sanger WG, Kessinger A, Armitage JO

Abstract

Philadelphia chromosome-positive acute myeloid leukemia (Ph(+)-AML) has a poor response to anthracycline- and cytarabine-containing regimens, high relapse rate, and dismal prognosis. Although therapy with imatinib and allogeneic stem cell transplantation (allo-SCT) is promising, relatively short follow-up limits understanding of long-term results of these therapies. This report describes the outcomes of 3 cases of Ph(+)-AML diagnosed and transplanted at the University of Nebraska Medical Center between 2004 and 2011. These patients, young and without major comorbidities, received induction therapy with 7 days of cytarabine and 3 days of idarubicin along with imatinib and consolidation therapy with high-dose cytarabine (with or without imatinib). All patients underwent 10/10 HLA-matched peripheral blood allo-SCT (sibling donor for first and third patients and unrelated donor for the second patient; all had acute graft-versus-host disease (GVHD), and the first and third patients had chronic GVHD. All patients are currently alive and experiencing complete remission at 116, 113, and 28 months after diagnosis, respectively. This report shows that the use of allo-SCT with resultant graft-versus-leukemia effect and the addition of imatinib can result in long-term remission and possible cure in some patients with Ph(+)-AML.

PMID: 24994916 [PubMed - indexed for MEDLINE]

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A dimorphic blast population demonstrates Philadelphia-positive mixed phenotype acute leukaemia.

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A dimorphic blast population demonstrates Philadelphia-positive mixed phenotype acute leukaemia.

Pathology. 2014 Apr;46(3):244-6

Authors: Ling VY, Wall M, Davis A, Gorniak M, Grigoriadis G

PMID: 24614709 [PubMed - indexed for MEDLINE]

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A novel method for room temperature distribution and conservation of RNA and DNA reference materials for guaranteeing performance of molecular diagnostics in onco-hematology: a GBMHM study.

Posted by rob on April 15, 2015 under Uncategorized | Comments are off for this article

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A novel method for room temperature distribution and conservation of RNA and DNA reference materials for guaranteeing performance of molecular diagnostics in onco-hematology: a GBMHM study.

Clin Biochem. 2015 Apr 11;

Authors: Cayuela JM, Mauté C, Fabre AL, Nibourel O, Dulucq S, Delabesse E, Villarèse P, Hayette S, Mozziconacci MJ, Macintyre E, GBMHM

Abstract

OBJECTIVES: Performance of methods used for molecular diagnostics must be closely controlled by regular analysis of internal quality controls. However, conditioning, shipping and long lasting storage of nucleic acid controls remain problematic. Therefore, we evaluated the minicapsules-based innovative process developed by Imagene (Evry, France) for implementing DNA and RNA controls designed for clonality assessment of lymphoproliferations and BCR-ABL1 mRNA quantification, respectively.

DESIGN & METHODS: DNA samples were extracted from 12 cell lines selected for giving specific amplifications with most BIOMED-2 PCR tubes. RNA samples were extracted from 8 cell line mixtures expressing various BCR-ABL1 transcript levels. DNA and RNA were encapsulated by Imagene and shipped at room temperature to participating laboratories. Biologists were asked to report quality data of recovered nucleic acids as well as PCR results.

RESULTS: Encapsulated nucleic acids samples were easily and efficiently recovered from minicapsules. The expected rearrangements at immunoglobulin, T-cell receptor and BCL2 loci were detected in DNA samples by all laboratories. Quality of RNA was consistent between laboratories and met the criteria requested for quantification of BCR-ABL1 transcripts. Expression levels measured by the 5 laboratories were within±2 fold interval from the corresponding pre-encapsulation reference value. Moreover aging studies of encapsulated RNA simulating up to 100years storage at room temperature show no bias in quantitative outcome.

CONCLUSIONS: Therefore, Imagene minicapsules are suitable for storage and distribution at room temperature of genetic material designed for proficiency control of molecular diagnostic methods based on end point or real-time quantitative PCR.

PMID: 25872147 [PubMed - as supplied by publisher]

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CD33-targeted lipid nanoparticles (aCD33LNs) for therapeutic delivery of GTI-2040 to acute myelogenous leukemia.

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CD33-targeted lipid nanoparticles (aCD33LNs) for therapeutic delivery of GTI-2040 to acute myelogenous leukemia.

Mol Pharm. 2015 Apr 14;

Authors: Li H, Xu S, Quan J, Yung BC, Pang J, Zhou C, Cho YA, Zhang M, Liu S, Muthusamy N, Chan KK, Byrd JC, Lee LJ, Marcucci G, Lee RJ

Abstract

CD33-targeted lipid nanoparticles (aCD33LNs) were synthesized for delivery of GTI-2040, an antisense oligonucleotide (ASO) against the R2 subunit of ribonucleotide reductase, to acute myelogenous leukemia (AML). These LNs incorporated a deoxycholate-polyethylenimine (DOC-PEI) conjugate, which has shown significant activity to facilitate oligonucleotide delivery. Anti-CD33 scFv (aCD33) was added as a targeting ligand. The delivery efficiency of this system was investigated both in vitro and in vivo. When cells were treated with aCD33LN/GTI-2040, significant uptake was observed in CD33 positive Kasumi-1 cells. aCD33LNs loaded with GTI-2040 induced significant down-regulation of R2 mRNA and protein levels in AML cells. Moreover, aCD33LN/GTI-2040 showed a 15-fold reduction in the IC50 of anti-leukemic drug Ara-C in Kasumi-1 cells. In Kasumi-1 xenograft model, aCD33LN/GTI-2040 showed significant R2 downregulation compared to LN/GTI-2040. Furthermore, aCD33LN/GTI-2040 co-administered with Ara-C was shown to be highly effective in tumor growth inhibition and to greatly increase survival time of mice bearing Kasumi-1 xenograft tumors. The conjugate DOC-PEI has shown an ability to include calcein release from lipid nanoparticles, suggests a potential mechanism contributing to efficient endosome release by DOC-PEI2K. These results indicate that aCD33LNs are a highly effective vehicle for the therapeutic delivery of antisense agents to AML.

PMID: 25871632 [PubMed - as supplied by publisher]

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Imatinib Mesylate Dose Adjustment Based on Body Surface Area for CML Chronic Phase Patients Intolerant to Standard Dosage.

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Imatinib Mesylate Dose Adjustment Based on Body Surface Area for CML Chronic Phase Patients Intolerant to Standard Dosage.

Acta Haematol. 2015 Apr 11;134(1):59-68

Authors: Sung HJ, Lee SR, Choi IK, Park Y, Choi CW, Kim HJ, Yhim HY, Kim BS

Abstract

AIM: Chronic myelogenous leukemia (CML) chronic phase (CP) patients cannot tolerate a standard dose (400 mg/day) of imatinib mesylate (IM), sometimes needing a reduced dose. This study aimed to find convenient clinical indexes, rather than plasma trough levels of IM, to define the appropriate IM dosage.

METHODS: Seventy CML CP patients who experienced an IM dose reduction, or a temporary cessation, were enrolled from 2002 to 2010. The IM treatment was resumed and maintained at either ?400 mg in 25 patients (35.7%; group ?400 mg) or at ?300 mg in 45 patients (64.3%; group ?300 mg). The various clinical characteristics of these patients were evaluated. The plasma trough level of IM was monitored in 20 patients from group ?300 mg.

RESULTS: Via multivariate analysis, the IM dosage divided by the body surface area (BSA) was an important index, presupposing a complete cytogenetic response at 12 months (CCyR12). Patients with IM/BSA >206.7 mg/m(2) showed a higher probability of CCyR12 than others. The IM/BSA (221.7 mg/m(2)) in group ?300 mg was higher than in group ?400 mg (207.6 mg/m(2)). The sustained response and survival rate of group ?300 mg was comparable to that of group ?400 mg. The plasma trough level of IM was significantly correlated with the IM/BSA.

CONCLUSION: Our study suggests that IM dose adjustments, based on IM/BSA, could improve the clinical outcomes in CML CP patients. © 2015 S. Karger AG, Basel.

PMID: 25871321 [PubMed - as supplied by publisher]

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Reliability Evaluation of Fluorescence In Situ Hybridization (FISH) and G-Banding on Bone Marrow and Peripheral Blood Cells in Chronic Myelogenous Leukemia Patients.

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Reliability Evaluation of Fluorescence In Situ Hybridization (FISH) and G-Banding on Bone Marrow and Peripheral Blood Cells in Chronic Myelogenous Leukemia Patients.

Cell J. 2015;17(1):171-80

Authors: Manaflouyan Khajehmarjany S, Rahmani SA, Chavoshi SH, Esfahani A, Movassaghpour Akbari AA

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative disease. The cytogenetic hallmark of CML is Philadelphia (Ph) chromosome. This study aimed to diagnose suspected CML patients, to monitor CML patients under therapy using cytogenetic and fluorescence in situ hybridization (FISH) techniques to analyze their bone marrow (BM) and peripheral blood (PB) samples, and finally to compare their obtained results for both specimens. This study was conducted during one-year period (2012-2013). The participants were recruited from the Hematology and Oncology Clinic of Shahid Gazi (Emam Reza) Hospital of Tabriz University of Medical Sciences, Tabriz, East Azerbaijan Province, Iran. We analyzed 90 samples from 60 suspected CML patients (30 BM and 60 PB samples). All samples were analyzed using G-banding, 5 samples using dual fusion FISH (DF-FISH) probes, as well as 30 samples using both FISH and G-banding. Among the 90 analyzed samples of 60 patients, 25 (41.66%) were Ph+ using karyotyping, whereas five cases were not analyzable, so FISH was applied and the results confirmed that only two individuals were BCR-ABL+. In the comparison between 25 BM and 25 PB samples using karyotyping, 15 (60%) and 10 (40%) were ph+, respectively. The comparison of FISH and karyotyping on 30 samples showed that 9 (30%) and 8 (26.66%) were Ph+, respectively, and only 18.18% of Ph+ patients showed atypical patterns. In the comparison between BM-cytogenetic and PB- interphase-FISH (I-FISH), BM-cytogenetic was more reliable than PB-I-FISH in detecting Ph. Our data demonstrate that FISH analysis is a rapid, reliable and sensitive technique. The comparison between BM and PB showed that PB can not be replaced by BM, even in detecting by FISH.

PMID: 25870848 [PubMed]

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Application of systematic coronary risk evaluation chart to identify chronic myeloid leukemia patients at risk of cardiovascular diseases during nilotinib treatment.

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Application of systematic coronary risk evaluation chart to identify chronic myeloid leukemia patients at risk of cardiovascular diseases during nilotinib treatment.

Ann Hematol. 2015 Mar;94(3):393-7

Authors: Breccia M, Molica M, Zacheo I, Serrao A, Alimena G

Abstract

Nilotinib is currently approved for the treatment of chronic myeloid leukemia (CML) in chronic (CP) and accelerated phase (AP) after failure of imatinib and in newly diagnosed patients. Atherosclerotic events were retrospectively reported in patients with baseline cardiovascular risk factors during nilotinib treatment. We estimated the risk of developing atherosclerotic events in patients treated with second or first-line nilotinib, with a median follow-up of 48 months, by retrospectively applying the SCORE chart proposed by the European Society of Cardiology (ESC) and evaluating risk factors at baseline (diabetes, obesity, smoking, and hypertension). Overall, we enrolled in the study 82 CP patients treated frontline (42 CP patients at the dose of 600 mg BID) or after failure of other tyrosine kinase inhibitors (40 CP patients treated with 400 mg BID). The SCORE chart is based on the stratification of sex (male vs female), age (from 40 to 65 years), smoker vs non-smoker, systolic pressure (from 120 to 180 mm Hg), and cholesterol (measured in mmol/l, from 150 to 300 mg/dl). For statistical purposes, we considered patients subdivided in low, moderate, high (with a score >5), and very high risk. There were 48 males and 34 females, median age 51 years (range 22-84). According to WHO classification, 42 patients were classified as normal weight (BMI <25), 26 patients were overweight (BMI 26???30), and 14 were obese (BMI >30). Retrospective classification according to the SCORE chart revealed that 27 patients (33 %) were in the low-risk category, 30 patients (36 %) in the moderate risk category, and 24 patients (29 %) in the high risk. As regards risk factors, we revealed that 17 patients (20.7 %) had a concomitant type II controlled diabetes (without organ damage), 23 patients (28 %) were smokers, 29 patients (35 %) were receiving concomitant drugs for hypertension, and 15 patients (18 %) had concomitant dyslipidemia. Overall, the cumulative incidence of atherosclerotic events at 48 months was 8.5 % (95 % CI, 4.55-14.07): None of the low-risk patients according to the SCORE chart experienced atherosclerotic events compared to 10 % in the moderate risk category and 29 % in the high risk (p?=?0.002). Atherosclerotic-free survival was 100, 89, and 69 % in the low, moderate, and high-risk population, respectively (p?=?0.001). SCORE chart evaluation at disease baseline could be a valid tool to identify patients at high risk of atherosclerotic events during nilotinib treatment.

PMID: 25304102 [PubMed - indexed for MEDLINE]

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[Chronic myeloid leukemia treatment and human immunodeficiency virus infection].

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[Chronic myeloid leukemia treatment and human immunodeficiency virus infection].

Rev Clin Esp (Barc). 2014 May;214(4):231-2

Authors: Campillo-Recio D, Perez-Rodriguez L, Yebra E, Cervero-Jimenez M

PMID: 24564991 [PubMed - indexed for MEDLINE]

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The clinical impact of ponatinib on the risk of bleeding in patients with chronic myeloid leukemia.

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The clinical impact of ponatinib on the risk of bleeding in patients with chronic myeloid leukemia.

Haematologica. 2013 Oct;98(10):e131

Authors: Nazha A, Romo CG, Kantarjian H, Cortes J

PMID: 24091930 [PubMed - indexed for MEDLINE]

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Platelet dysfunction associated with ponatinib, a new pan BCR-ABL inhibitor with efficacy for chronic myeloid leukemia resistant to multiple tyrosine kinase inhibitor therapy.

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Platelet dysfunction associated with ponatinib, a new pan BCR-ABL inhibitor with efficacy for chronic myeloid leukemia resistant to multiple tyrosine kinase inhibitor therapy.

Haematologica. 2012 Sep;97(9):1444

Authors: Neelakantan P, Marin D, Laffan M, Goldman J, Apperley J, Milojkovic D

PMID: 22532521 [PubMed - indexed for MEDLINE]

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Hearing Loss in Palliative Care.

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Hearing Loss in Palliative Care.

J Palliat Med. 2015 Apr 13;

Authors: Smith AK, Jain N, Wallhagen ML

Abstract

BACKGROUND: Age-related hearing loss is remarkably common, affecting more than 60% of adults over the age of 75. Moreover, hearing loss has detrimental effects on quality of life and communication, outcomes that are central to palliative care. Despite its high prevalence, there is remarkably little written on the impact of hearing loss in the palliative care literature.

OBJECTIVE: The objective was to emphasize its importance and the need for further study. We use a case as a springboard for discussing what is known and unknown about the epidemiology, presentation, screening methodologies, and treatment strategies for age-related hearing loss in palliative care.

DISCUSSION: The case describes a 65-year-old man with acute myelogenous leukemia (AML) that has progressed despite treatment. No concerns are raised about communication challenges during conversations between the palliative care team and the patient in his quiet room. However, in the midst of a family meeting, shortly after discussing prognosis, the patient reports that he cannot hear what anyone is saying.

CONCLUSION: We describe simple methods of screening patients for hearing loss, and suggest that practical approaches should be used universally in patient encounters. These include facing the patient, pitching one’s voice low, using a pocket talker, and creating a hearing-friendly environment when planning a family or group meeting.

PMID: 25867966 [PubMed - as supplied by publisher]

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[Bone marrow microenvironment in chronic myeloid leukemia: implications for disease physiopathology and response to treatment].

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[Bone marrow microenvironment in chronic myeloid leukemia: implications for disease physiopathology and response to treatment].

Rev Med Chil. 2014 May;142(5):599-605

Authors: Aristizábal JA, Chandia M, Del Cañizo MC, Sánchez-Guijo F

Abstract

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm related to the presence of the BCR-ABL1 fusion gene, linked to t (9;22) (q34;q11). It is originated from an abnormal hematopoietic stem cell, which is characterized as its normal counterparts by long-term self-renewal and multi-lineage differentiation. Both leukemic and quiescent normal hematopoietic stem cells preferentially reside in the osteoblastic niche. Mesenchymal stromal cells (MSC) are located near them, playing a critical role in their regulation. Currently, with tyrosine kinase inhibitor (TKI) therapy, long term clinical responses are achieved in most CML cases. However, late treatment failures may be observed related to the persistence of leukemic stem cells. The interactions between the leukemic stem cell and the microenvironment may be responsible in part for these events. We review the interactions between the leukemic stem cell and BM stroma and its potential clinical and therapeutic implications.

PMID: 25427017 [PubMed - indexed for MEDLINE]

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Molecular monitoring to improve outcomes in patients with chronic myeloid leukemia in chronic phase: importance of achieving treatment-free remission.

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Molecular monitoring to improve outcomes in patients with chronic myeloid leukemia in chronic phase: importance of achieving treatment-free remission.

Am J Hematol. 2015 Mar;90(3):242-9

Authors: Erba HP

Abstract

Imatinib was the first BCR-ABL1 tyrosine kinase inhibitor (TKI) developed for the treatment of patients with chronic myeloid leukemia (CML); subsequently, the introduction of more potent BCR-ABL1 TKIs has raised expectations regarding the speed and depth of response. This review discusses how molecular monitoring is being used as an integral part of the treatment regimen to achieve improved outcomes in patients with CML. The long-term prognostic implications of achieving early molecular response to TKI therapy and the feasibility of maintaining treatment-free remission will also be discussed in light of current clinical data.

PMID: 25410137 [PubMed - indexed for MEDLINE]

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Role of the hybrid Bcr/Abl kinase in the pathogenesis of chronic myeloid leukemia lacking C-Abl and CXCR4 proteins.

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Role of the hybrid Bcr/Abl kinase in the pathogenesis of chronic myeloid leukemia lacking C-Abl and CXCR4 proteins.

Exp Oncol. 2014 Sep;36(3):138-43

Authors: Polishchuk LA, Telegeev GD

Abstract

Philadelphia chromosome is a result of chromosomal rearrangement that leads to the appearing of the hybrid gene bcr/abl. A hybrid mRNA transcribes from bcr-promoter and many copies of hybrid molecules of Bcr/Abl protein are formed as a result of bcr/abl gene expression. It is supposed that a hybrid Abl molecule, replacing the normal one, in majority of cases functions abnormally or does not function at all. Also it is possible that Abl moiety of Bcr/Abl protein which is possibly recognized by some hypothetical cell control system interpreted by cell as an overproduction of c-abl. This, probably, leads to blocking the normal C-Abl molecules production from the normal c-abl gene transcribed from the second non-aberrant chromosome 9. Based on C-Abl physiological functions in conjunction with the most important proteins of which functions directly depend on its activity we tried to outline the research directions that might explain disruptions of the processes at chronic myeloleukosis such as cell migration due to CXCL12/CXCR4 axis activation, reparation, apoptosis, control for mitochondria state, and to propose new perspective therapeutic approaches based on all this knowledge.

PMID: 25265345 [PubMed - indexed for MEDLINE]

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Remission status should not be treated as a base-line covariate–reply to Etienne et al.

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Remission status should not be treated as a base-line covariate–reply to Etienne et al.

Haematologica. 2014 Sep;99(9):e174-5

Authors: Lauseker M, Hasford J

PMID: 25176984 [PubMed - indexed for MEDLINE]

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