Use of Real-World Claim Databases to Assess Prevalence of Comorbid Conditions Relevant to the Treatment of Chronic Myelogenous Leukemia Based on National Comprehensive Network Treatment Guidelines.
Clin Lymphoma Myeloma Leuk. 2015 Sep 30;
Authors: Jabbour E, Makenbaeva D, Lingohr-Smith M, Lin J
BACKGROUND: The National Comprehensive Cancer Network (NCCN) guidelines state that based on toxicity profiles, 1 second-generation tyrosine kinase inhibitor (TKI) indicated for first-line therapy (ie, dasatinib, nilotinib) may be preferred over the other for treatment of chronic myelogenous leukemia (CML) patients with certain comorbidities. This study assessed the prevalence of comorbid conditions relevant to TKI treatment choice among CML patients in the US real-world setting.
PATIENTS AND METHODS: Patients who had CML and initiated TKI treatment were identified from the MarketScan Commercial and Medicare databases (January 1, 2006, to June 30, 2013). Demographics and prevalence of comorbid conditions relevant to TKI treatment choice per NCCN guidelines (heart disease, arrhythmia, diabetes, pancreatitis, pleural effusion, lung disease) were assessed among the overall study population and among subgroups.
RESULTS: The median age of the CML study population newly initiated on TKI treatment (ie, imatinib, dasatinib, or nilotinib; n = 2296) was 56 years. Approximately 41% of the CML study population had at least 1 comorbid condition that may influence the choice of TKI treatment as recommended by NCCN guidelines. The most prevalent comorbid condition was heart disease (23%), followed by diabetes (18%) and lung disease (13%). The prevalence of comorbid conditions relevant to TKI treatment choice varied among patients of different age groups, gender, and US regions.
CONCLUSION: The results of this analysis provide real-world evidence that the prevalence of relevant comorbid conditions is substantial among CML patients in the US managed care setting and therefore needs to be considered throughout various health care decision-making processes related to CML.
PMID: 26603185 [PubMed - as supplied by publisher]
Thiarabine, 1-(4-Thio-?-D-arabinofuranosyl)cytosine. A Deoxycytidine Analog With Excellent Anticancer Activity.
Curr Med Chem. 2015;22(34):3881-96
Authors: Parker WB, Waud WR, Secrist JA
Thiarabine has demonstrated exceptional antitumor activity against numerous human tumor xenografts in mice, being superior to gemcitabine, clofarabine, or cytarabine. Unlike cytarabine, thiarabine demonstrated excellent activity against solid tumor xenografts, suggesting that this agent has the kind of robust activity in animal models that leads to clinical utility. Thiarabine is effective orally (bioavailability of approximately 16%) and with once per day dosing: Two characteristics that distinguish it from cytarabine. Although both the structure and basic mechanism of action of thiarabine are similar to that of cytarabine, there are many quantitative differences in the biochemical pharmacology of these two agents that can explain the superior antitumor activity of thiarabine. Two important attributes are the long retention time of the 5′-triphosphate of thiarabine in tumor cells and its potent inhibition of DNA synthesis. The biochemical pharmacology of thiarabine is also different from that of gemcitabine. Thiarabine has been evaluated in three phase I clinical trials, where it has demonstrated some activity in heavily pretreated patients with hematologic malignancies and solid tumors. Because of its impressive activity against numerous human tumor xenografts in mice, its unique biochemical activity, and encouraging clinical results in phase I clinical trials, we believe thiarabine should continue to be evaluated in the clinic for treatment of hematologic and/or solid tumors. The preclinical results to date (superior in vivo antitumor activity, oral bioavailability, and once per day dosing), suggest that thiarabine could replace cytarabine in the treatment of acute myelogenous leukemia.
PMID: 26597061 [PubMed - in process]
Inhibition of pentose phosphate pathway suppresses acute myelogenous leukemia.
Tumour Biol. 2015 Nov 23;
Authors: Chen Y, Xu Q, Ji D, Wei Y, Chen H, Li T, Wan B, Yuan L, Huang R, Chen G
Pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentose. PPP genes have been reported to be primarily or secondarily upregulated in many cancers. We aimed to study the general alteration of PPP in acute myelogenous leukemia (AML). We performed data mining and analysis of the Cancer Genome Atlas (TCGA) AML dataset for genetic alteration of the PPP gene set. In vitro studies including proliferation, migration, and invasion assays, together with metabolite consumption and oxidation assays, were performed. PPP genes were upregulated in 61 % of patients with AML. The majority of altered cases were expression changes measured by RNA sequencing. Expressions of critical PPP genes such as G6PD, PFKL, PFKP, and PGLS were consistently upregulated in all altered cases. Altered PPP is not associated with survival or disease relapse. PPP inhibition using 6-aminonicotinamide (6AN) increases glucose oxidative metabolism in AML. 6AN decreased the glucose oxidation and increased fatty acid oxidation. Here, we showed that PPP inhibition increased glucose oxidative metabolism in AML. PPP inhibition suppressed growth, migration, and invasion of AML, but not colony formation. PPP plays an important role in AML. Our results could contribute to the development of novel targeted treatment.
PMID: 26596840 [PubMed - as supplied by publisher]
[Sudden deafness as the initial manifestation of chronic myelogenous leukemia: case report].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2015 May;29(10):952-3
Authors: Chen Y, An L, Jin G
To study the pathogenesis of hearing loss in chronic myelogenous leukemia (CML). To report one case with CML whose first sign was sudden unilateral hearing loss. Sudden hearing loss in CML was presented with dramatic high white blood cell count in peripheral blood. Some cases of sudden hearing loss in CML may be improved or even cured by leukapheresis and intrathecal chemotherapy. The proposed pathogenesis for deafness in leukemia is due to hyperleukocytosis, hyperviscosity syndrome, leukemic infiltration and the inner ear hemorrhage. In treatment, clinicians should quickly reduce the number of white blood cells to lighten the tumor burden. Intrathecal injection of MTX and plasmapheresis is commonly used.
PMID: 26596019 [PubMed - in process]
Performance of two commercially available BCR-ABL1 quantification assays that use an international reporting scale.
Clin Chem Lab Med. 2015 Nov 20;
Authors: Seo SH, Lee SJ, Park S, Kim MJ, Song JY, Ra EK, Cho SI, Kim HK, Yang MG, Kim JY, Park SS, Seong MW
BACKGROUND: Quantifying the BCR-ABL1 rearrangement is important for monitoring chronic myelogenous leukemia (CML). To standardize BCR-ABL1 quantification, the World Health Organization (WHO) established the first international genetic reference panel. Here, we compared the BCR-ABL1 levels determined using international scale (IS)-based commercially available assays.
METHODS: BCR-ABL1 transcripts were quantified using two IS-based assays. 10-1, 10-2, 10-3, 10-4, 10-5 and 10-6 dilutions of the b3a2 positive RNA were used for evaluating linearity, precision, and limit of detection. Correlation of the assay was evaluated by using DNA obtained from CML patients carrying the BCR-ABL1 b3a2 and b2a2 types.
RESULTS: Both Ipsogen and Asuragen assays showed fine linearity with reasonable %CV. LOD of each assay was calculated as 0.003% for Ipsogen, and 0.005% for Asuragen. By comparing the results that were lower than 10% by either one of the assay, Ipsogen and Asuragen results showed an overall good linear correlation with a tendency for the Ipsogen assay to show slightly higher levels than the Asuragen assay for b3a2 transcript. For b2a2, the tendency was opposite, with Asuragen showing higher values than the Ipsogen.
CONCLUSIONS: Two commercially available IS-based BCR-ABL1 assays showed an overall good quantitative correlation. It should be taken into consideration that each assay tended to produce higher values than the other, depending on the BCR-ABL1 subtypes, suggesting that a separate conversion factor for each subtype can be more helpful when BCR-ABL1 transcript levels are converted into IS.
PMID: 26587743 [PubMed - as supplied by publisher]
The novel oral TGF-? signaling inhibitor EW-7197 eradicates chronic myelogenous leukemia-initiating cells.
Cancer Sci. 2015 Nov 19;
Authors: Naka K, Ishihara K, Jomen Y, Jin CH, Kim DH, Gu YK, Jeong ES, Li S, Krause DS, Kim DW, Bae E, Takihara Y, Hirao A, Oshima H, Oshima M, Ooshima A, Sheen YY, Kim SJ, Kim DK
Recent strategies for treating chronic myelogenous leukemia (CML) patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia-initiating cells (CML-LICs). However, little is known about the therapeutic benefits such CML-LIC targeting therapies might bring to CML patients. In this study, we investigated the therapeutic potential of EW-7197, an orally bioavailable TGF-? signaling inhibitor which has recently been approved as an Investigational New Drug (NIH, USA), to suppress CML-LICs in vivo. Compared to TKI treatment alone, administration of TKI plus EW-7197 to CML-affected mice significantly delayed disease relapse and prolonged survival. Notably, the combined administration of EW-7197 plus TKI was effective in eliminating CML-LICs even if they expressed the TKI-resistant T315I mutant BCR-ABL1 oncogene. Collectively, these results indicate that EW-7197 may be a promising candidate for a new therapeutic that can greatly benefit CML patients by working in combination with TKIs to eradicate CML-LICs. This article is protected by copyright. All rights reserved.
PMID: 26583567 [PubMed - as supplied by publisher]
Impact of Genetic Mutations and Health Plan Access to Therapies on Treatment Response and Drug Costs Related to Tyrosine Kinase Inhibitor Treatment Among Patients With Chronic Myelogenous Leukemia.
Am J Clin Oncol. 2015 Nov 17;
Authors: Jabbour E, Makenbaeva D, Lingohr-Smith M, Lin J
OBJECTIVES: This study assessed treatment responses and economic consequences of limiting access to the second-generation BCR-ABL1 tyrosine kinase inhibitors (2G-TKI), dasatinib and nilotinib, for treatment of chronic myelogenous leukemia, while taking into account frequencies of genetic mutations that exhibit different sensitivities to the 2G-TKIs.
METHODS: Frequencies of BCR-ABL1 mutations and the impact of mutations on responses to 2G-TKIs were obtained from published literature and used as inputs in a decision analytics model. Complete hematologic response (CHR) and major cytogenetic response (MCyR) were estimated after 12 months of 2G-TKI treatment. Total annual 2G-TKI drug costs per CHR and MCyR were estimated and compared among 3 2G-TKI access scenarios: (1) open access to both 2G-TKIs; (2) access restricted to dasatinib (DASA-only); and (3) access restricted to nilotinib (NILO-only).
RESULTS: Among a hypothetical cohort of 1000 2G-TKI-treated chronic myelogenous leukemia patients, the percentage of patients with CHR and MCyR were greatest for the open access plan (CHR: 93%, MCyR: 56%), followed by DASA-only (88%, 53%) and NILO-only (67%, 47%). Compared with the 2G-TKI costs per CHR in open access ($120,706/CHR), the costs were 5% higher ($126,753/CHR) in DASA-only and 41% higher ($169,990/CHR) in NILO-only. Likewise, compared with the 2G-TKI costs per MCyR in open access ($198,284/MCyR), the costs were 6% higher ($209,259/MCyR) in DASA-only and 22% higher ($241,515/MCyR) in NILO-only.
CONCLUSION: Open access to both 2G-TKIs is associated with improved clinical and economic outcomes: greater treatment response rates (CHR and MCyR) and lower drug costs compared with restricted access to 2G-TKIs.
PMID: 26580245 [PubMed - as supplied by publisher]
Mechanisms of resistance to EGFR tyrosine kinase inhibitors.
Acta Pharm Sin B. 2015 Sep;5(5):390-401
Authors: Huang L, Fu L
Since the discovery that non-small cell lung cancer (NSCLC) is driven by epidermal growth factor receptor (EGFR) mutations, the EGFR tyrosine kinase inhibitors (EGFR-TKIs, e.g., gefitinib and elrotinib) have been effectively used for clinical treatment. However, patients eventually develop drug resistance. Resistance to EGFR-TKIs is inevitable due to various mechanisms, such as the secondary mutation (T790M), activation of alternative pathways (c-Met, HGF, AXL), aberrance of the downstream pathways (K-RAS mutations, loss of PTEN), impairment of the EGFR-TKIs-mediated apoptosis pathway (BCL2-like 11/BIM deletion polymorphism), histologic transformation, ATP binding cassette (ABC) transporter effusion, etc. Here we review and summarize the known resistant mechanisms to EGFR-TKIs and provide potential targets for development of new therapeutic strategies.
PMID: 26579470 [PubMed - as supplied by publisher]
BCR-ABL1 e6a2 transcript in chronic myeloid leukemia: biological features and molecular monitoring by droplet digital PCR.
Virchows Arch. 2015 Sep;467(3):357-63
Authors: Zagaria A, Anelli L, Coccaro N, Tota G, Casieri P, Cellamare A, Impera L, Brunetti C, Minervini A, Minervini CF, Delia M, Cumbo C, Orsini P, Specchia G, Albano F
The BCR-ABL1 fusion on the Philadelphia (Ph) chromosome is a hallmark of chronic myeloid leukemia (CML). More than 95 % of BCR-ABL1 transcripts in CML are either e13a2 or e14a2 (major breakpoint cluster region or M-bcr), whereas rare BCR-ABL1 transcripts are occasionally observed, accounting for less than 1 % of CML cases. Among these, a very rare fusion transcript joining the first 6 exons of BCR to exon 2 of ABL1 (e6a2) has been reported in various hematological malignancies characterized by an aggressive clinical course. We report a new case of blast crisis (BC) CML with an e6a2 fusion transcript characterized by many eosinophil precursors with abnormal granules. Moreover, fluorescence in situ hybridization analysis revealed genomic deletions of 1.3 megabases and 342 kilobases on der(9) of chromosome 9 and 22 sequences, respectively. The fusion transcript was quantified at diagnosis and during follow-up using digital droplet polymerase chain reaction (ddPCR) technology. The patient was treated with Dasatinib (140 mg/day), resulting in a 3-log reduction of the e6a2 transcript molecular burden from the third month after treatment. In this twentieth e6a2 case, characterized by marked eosinophilic dysplasia, deletions on der(9), and responsive to tyrosine kinase inhibitors therapy, we demonstrate that for molecular response monitoring of rare fusion transcripts associated with CML, ddPCR is a very useful technology.
PMID: 26149409 [PubMed - indexed for MEDLINE]
Safety of a second-generation tyrosine kinase inhibitor and novel targeted therapy for the treatment of a patient with chronic myeloid leukemia and multiple myeloma.
Anticancer Drugs. 2015 Sep;26(8):907-9
Authors: Katzel JA, Lee-Ma A, Vesole DH
The prevalence of chronic myeloid leukemia and multiple myeloma has increased in recent years partly because of an improved therapeutic armamentarium for both conditions. Likewise, understanding the complexity inherent in designing combination treatment strategies will become increasingly prescient in the coming years. We describe, to the best of our knowledge, the first reported patient to be treated with second-generation tyrosine kinase inhibitor therapy while on novel therapy for myeloma. The combination was well tolerated and effective for the treatment of chronic myeloid leukemia and concurrent myeloma.
PMID: 26111050 [PubMed - indexed for MEDLINE]
The downregulation of BAP1 expression by BCR-ABL reduces the stability of BRCA1 in chronic myeloid leukemia.
Exp Hematol. 2015 Sep;43(9):775-80
Authors: Dkhissi F, Aggoune D, Pontis J, Sorel N, Piccirilli N, LeCorf A, Guilhot F, Chomel JC, Ait-Si-Ali S, Turhan AG
BCR-ABL induces an intrinsic genetic instability in chronic myeloid leukemia (CML). The protein breast cancer 1, early onset (BRCA1)-associated protein 1 (BAP1) is a deubiquitinase interacting with the DNA repair regulator BRCA1 and is frequently inactivated in many cancers. Here, we report that BAP1 mRNA and protein levels are downregulated in a BCR-ABL1-expressing hematopoietic cell line (UT-7/11). A decrease of BAP1 transcripts is also observed in newly diagnosed CML patients. Moreover, BAP1 protein levels are low or undetectable in CD34(+) cells from CML patients at diagnosis as compared with CD34(+) cells from normal donors. In addition, BRCA1 protein level is reduced in BCR-ABL1-expressing UT-7/11 cells. Finally, the enforced expression of BAP1 is associated with BRCA1 protein deubiquitination and restoration. These results demonstrate BAP1 as a major link with the BCR-ABL-induced downregulation of BRCA1 in CML.
PMID: 26118501 [PubMed - indexed for MEDLINE]
[Dasatinib-related pneumonia? An example of pharmacovigilance survey].
Rev Mal Respir. 2015 Jan;32(1):84-6
Authors: Audemard A, de la Gastine B, Chantepie S, Verger H, Gac AC, Bergot E, Reman O
PMID: 25618211 [PubMed - indexed for MEDLINE]
Inhibition of euchromatic histone methyltransferase 1 and 2 sensitizes chronic myeloid leukemia cells to interferon treatment.
PLoS One. 2014;9(7):e103915
Authors: Loh SW, Ng WL, Yeo KS, Lim YY, Ea CK
BACKGROUND: H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.
RESULTS: We report the application of EHMT1 and EHMT2 specific chemical inhibitors to sensitize CML cell lines to interferon and imatinib treatments. Inhibition of EHMT1 and EHMT2 with BIX01294 enhances the cytotoxicity of IFN?2a in four CML cell lines, K562, KCL22, BV173 and KT1 cells. Chromatin immunoprecipitation assay shows that BIX01294 treatment enhances type I interferon response by reducing H3K9me2 at the promoters of interferon-stimulated genes. Additionally, BIX01294 treatment augments IFN?2a- and imatinib-mediated apoptosis in CML cell lines. Moreover, our data suggest that the expression level of EHMT1 and EHMT2 inversely correlates with the type I interferon responsiveness in CML cell lines.
CONCLUSIONS: Our study sheds light on the role of EHMT1 and EHMT2 as potential targets in improving the efficacy of standard treatments of CML.
PMID: 25079219 [PubMed - indexed for MEDLINE]
Development of Alkyne-Containing Pyrazolopyrimidines to Overcome Drug Resistance of Bcr-Abl Kinase.
J Med Chem. 2015 Nov 12;
Authors: Zhang C, Kung A, Liu X, Prakash GK, Malinoski B
Despite the success of imatinib at inhibiting Bcr-Abl and treating chronic myelogenous leukemia (CML), resistance to the therapy occurs over time in the patients. In particular, the resistance to imatinib caused by the gatekeeper mutation T315I in Bcr-Abl remains a challenge in the clinic. Inspired by the successful development of ponatinib to curb drug resistance, we hypothesize that the incorporation of an alkyne linker in other heterocyclic scaffolds can also achieve potent inhibition of Bcr-AblT315I by allowing for simultaneous occupancy of both the active site and the allosteric pocket in the Abl kinase domain. Herein, we describe the design, synthesis, and characterization of a series of alkyne-containing pyrazolopyrimidines as Bcr-Abl inhibitors. Our results demonstrate that some alkyne-containing pyrazolopyrimidines potently inhibit not only AblT315I in vitro, but also Bcr-AblT315I in cells. These pyrazolopyrimidines can serve as lead compounds for future development of novel targeted therapy to overcome drug resistance of CML.
PMID: 26562217 [PubMed - as supplied by publisher]
Acute colitis presenting with hematochezia in a patient with chronic myeloid leukemia during dasatinib therapy.
Turk J Gastroenterol. 2014 Dec;25 Suppl 1:233
Authors: Eskazan AE, Hatemi ?, Öngören Ayd?n S, Ar MC, Soysal T
PMID: 25910316 [PubMed - indexed for MEDLINE]
Another piece of the puzzle–optimal TKI selection before treatment discontinuation in CML.
Eur J Haematol. 2015 Mar;94(3):189-90
Authors: Wolf D
PMID: 25712068 [PubMed - indexed for MEDLINE]
Dasatinib induces fast and deep responses in newly diagnosed chronic myeloid leukaemia patients in chronic phase: clinical results from a randomised phase-2 study (NordCML006).
Eur J Haematol. 2015 Mar;94(3):243-50
Authors: Hjorth-Hansen H, Stenke L, Söderlund S, Dreimane A, Ehrencrona H, Gedde-Dahl T, Gjertsen BT, Höglund M, Koskenvesa P, Lotfi K, Majeed W, Markevärn B, Ohm L, Olsson-Strömberg U, Remes K, Suominen M, Simonsson B, Porkka K, Mustjoki S, Richter J, Nordic CML Study Group
We randomised 46 newly diagnosed patients with chronic myeloid leukaemia (median age 56) to receive dasatinib 100 mg QD or imatinib 400 mg QD and report outcome as an intention-to-treat analysis with 36 months follow-up. Early cytogenetic and molecular responses were superior in the dasatinib group, with a tendency that imatinib patients caught up with time. For instance, MR(3.0) was reached at 3 months in 36% vs. 8% (P = 0.02), at 12 months in 81% vs. 46% (P = 0.02) and at 18 months in 73% vs. 65% (n.s.) of the patients in the two groups. In contrast, MR(4.5) was consistently superior in the dasatinib group at all time points from 6 months onwards, reaching 61% vs. 21% (P < 0.05) at 36 months. Sixty-four vs. 71% of the patients in the dasatinib and imatinib arms, respectively, remained on assigned drug. Dasatinib dose was frequently reduced, but with maintained excellent effect. One imatinib patient progressed to blastic phase, but no CML-related deaths occurred. In conclusion, our data compare favourably with those of the dasatinib registration study, DASISION. The fast and deep molecular responses induced by dasatinib compared with imatinib may be exploited to increase the proportion of patients who can achieve a treatment-free remission after treatment discontinuation.
PMID: 25082346 [PubMed - indexed for MEDLINE]
Cultural factors related to adherence to imatinib in CML: a Mexican perspective.
Hematology. 2015 Mar;20(2):72-6
Authors: Cantú-Rodríguez OG, Sánchez-Cárdenas M, Gutiérrez-Aguirre CH, Jaime-Pérez JC, Mancias-Guerra C, González-Llano O, Gómez-Almaguer D
INTRODUCTION: The advent of imatinib as a therapeutic option of chronic myeloid leukemia (CML) has transformed this previously highly resistant disease into one that is susceptible to management with oral drugs that now offer high long-term survival rates. However, achieving an adequate adherence to treatment regimes is of critical importance. The characteristics of treatment compliance in Mexican patients have not been determined.
METHODS: We evaluated 38 CML patients, members of the Glivec(®) International Patient Assistance Program (GIPAP). A bimonthly simplified medication adherence questionnaire was applied and the adherence rate was calculated by direct tablet counting.
RESULTS: Two groups, one of local patients and another of out-of-town patients, were studied using an 85% adherence rate as a cut-off. The overall adherence rate was 85.9%. Fifteen patients were considered non-adherent (39.5%). The group of out-of-town patients presented a higher adherence rate of 92.8% in contrast with 76.3% in the local population (P = 0.021). The probability of achieving a complete cytogenetic response at some point of evolution after 8 years of follow-up was 93% in the adherent group vs. 58% in the group with an adherence rate <85% (P = 0.008). In patients with imatinib failure, the adherence rate was 75.8% compared to 95.5% (P = 0.008) in the optimal response group.
CONCLUSIONS: In Mexican patients with CML, non-adherence to treatment is a cause of the failure to achieve remission or the subsequent loss of a complete cytogenetic and major molecular response.
PMID: 25034734 [PubMed - indexed for MEDLINE]
Detection of BCR-ABL1 mutations that confer tyrosine kinase inhibitor resistance using massively parallel, next generation sequencing.
Ann Hematol. 2015 Nov 10;
Authors: Szankasi P, Schumacher JA, Kelley TW
Detection of BCR-ABL1 mutations that confer resistance to tyrosine kinase inhibitors is important for management of patients with t(9;22);BCR-ABL1-positive (Ph+) leukemias. Testing is often performed using Sanger sequencing (SS) which has relatively poor sensitivity. Given the widespread adoption of next generation sequencing (NGS), we sought to reevaluate the testing in the context of NGS methods. We developed an NGS-based BCR-ABL1 mutation test on the Ion Torrent Personal Genome Machine (PGM) to test for resistance mutations, primarily in the kinase domain in BCR-ABL1. We analyzed 508 clinical samples from patients with Ph+ leukemias. In a subset of these samples (n?=?97), we conducted a comparison of the NGS results to a classical SS-based test. NGS facilitated detection of low-level mutations (<20 % allele frequency) that were not detectable by SS. In a subset of cases with multiple mutations, NGS was also able to determine if two mutations were on the same molecule (compound) or on separate molecules (polyclonal) but this was limited by the distance between mutated positions and by the effects of apparent distance-dependent PCR recombination. We found 22 compound mutations that centered on one or two key residues including two novel compound mutants: Q252H/Y253H and F311Y/F359I. The advantages of NGS make it a superior method for inventorying BCR-ABL1 resistance mutations. However, data analysis may be complicated by short read lengths and the effects of PCR recombination.
PMID: 26555285 [PubMed - as supplied by publisher]
Sudden sensorineural hearing loss as the first manifestation of chronic myeloid leukaemia: case report.
J Laryngol Otol. 2014 Nov;128(11):1015-7
Authors: Diao M, Tian F, Sun J
BACKGROUND: Sudden sensorineural hearing loss rarely occurs in patients with chronic myeloid leukaemia.
CASE REPORT: We present a case report of a patient who presented with sudden sensorineural hearing loss as the first manifestation of chronic myeloid leukaemia, and review the mechanisms responsible for sudden sensorineural hearing loss in leukaemic patients.
RESULTS: A 31-year-old female presented to our clinic with unilateral sudden sensorineural hearing loss and tinnitus. Pure tone audiometry revealed profound sensorineural hearing loss in the left ear at all frequencies. During an investigation into her hearing loss, the patient was found to have chronic myeloid leukaemia.
CONCLUSION: Every case of sudden sensorineural hearing loss must be carefully evaluated, and haematological disorders must be considered in the differential diagnosis of sudden hearing loss.
PMID: 25399829 [PubMed - indexed for MEDLINE]