Identification of rare atypical BCR-ABL1 transcript: A case report

CML is characterized by the presence of a BCR-ABL1 fusion transcript. Several guidelines have been published for its detection and molecular monitoring. Here, a case is described of chronic myeloid leukemia presenting in the blast phase with a rare variant transcript, with a discussion on possible red flags in its detection and genetic testing and description of the patient's clinical characteristics. This case highlights the pitfalls of using real-time quantitative reverse-transcription polymerase chain reaction (RQ-PCR) for diagnosis of CML, especially when the clinical picture and the test results are discordant.

Response to Tyrosine Kinase Inhibitors in Patients with BCR-ABL1 Positive Chronic Myeloid Leukemia; 13.5 Years’ Experience at Patan Hospital, Nepal

Background:Since the advent of Tyrosine Kinase Inhibitor (TKI), well controlled studies in developed world have shown that the life expectancy of patients with CML is comparable to normal people without the disease. But long-term follow up studies are lacking in resource poor setting. Methods:This is a retrospective follow up study looking at the molecular response and resistance to Tyrosine Kinase Inhibitors (TKI) in patients enrolled in the Max Access Program since February 2003 till March 2017. Patients with twoor more BCR-ABL1 levels by Karyotyping/ fluorescent in situ hybridization (FISH) / reverse transcriptase polymerase chain reaction (RT-PCR) were included. At baseline, complete blood count (CBC), renal function test (RFT), and liver function test (LFT) were evaluated. Bone marrow aspiration and biopsy for morphology, cytogenetic analysis by Karyotyping/FISH and/or molecular analysis by RT-PCR were also done if these tests were not performed earlier. FISH or RT-PCR was done on peripheral blood every 3–12 months as necessary if the patient could afford. Patients with warning response/failure underwent BCR-ABL1 Resistance Mutation Analysis (IRMA).Results:Three hundred and forty six (346) patients had two or more BCR-ABL1 monitoring tests done. Optimal response was seen in 49.42%. Similarly, suboptimal response and failure were seen in 16.5% and 34% respectively. Overall Survival is 89.6% (at 1.8 -165 months, mean 62 months) . If only CML related events is considered survival is 95.9%. Seventy seven (77) patients with a total of 80 BCR-ABL1 domain Imatinib Resistance Mutation Analyses (IRMA) showed 19 different types of mutations with the most common being T315I mutation (8 and 19.5%). About 22.25% of the total patients showed resistance to Glivec out of which 10.98% showed mutations. Nine patients underwent trial for treatment free response (TFR) and 5 of them relapsed between 2-8 months.Conclusions:Despite all the odds of having financial problem, accessibility problem due to distances, transportation, etc. and difficulty monitoring with routine BCR-ABL1 and IRMA, our findings show that the outcome of TKI therapy in our CML patients is comparable to well controlled studies done elsewhere. Overall survival, molecular and cytogenetic responses and mutations in our patients who developed resistance as well as TFR are also similar to other studies. The resistance rate of 22.25% is slightly higher compared to other studies in developed world. This is mainly because of poor monitoring due to unavailability of the test including IRMA in our country and affordability until 2012. It proves that TKI is very effective in CML even in a resource-poor, developing country

To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia / 中华血液学杂志

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

Demographics and Overall Survival Pattern of Chronic Myeloid Leukemia in a Tertiary Hospital in South-South Nigeria: The Calabar Experience

Background: Chronic myeloid leukemia (CML) is a bi- or triphasic disease comprising of the chronic phase (present at diagnosis in approximately 85% of patients) which can easily be controlled with conventional chemotherapy, followed by unstable accelerated phase and terminating in a blastic phase. The treatment of CML has evolved over the years The availability of the tyrosine kinase inhibitors has distinctly changed the disease course for patients with Ph+ and/or BCR-ABL1+ (CML). This study aims to determine the demographics and overall survival patterns of CML patients in the University of Calabar Teaching Hospital (UCTH)l. Methods: The study is a retrospective study of twenty-two (22) CML patients seen and managed at the UCTH from June 2014 to August 2021. Male/female distribution was 9/13, with a median age of 42 years. Overall survival (OS) and progression free survival (PFS) were determined using the Kaplan-Meier techniques. The data were analyzed using Microsoft Excel 2016 and IBM SPSS version 21. Results: Total of 22 CML patients were seen over the 8-year-period of review. The mean age was 42.63, median age 42, and modal age was 37 years respectively. There were 9 males and 13 females. 20 of the patients were in the chronic phase while 2 were in the terminating blastic phase. The presence of mutation was seen in two patients while the remaining 20 showed no mutation. Of the patients, 6 were dead and 16 are alive at the time of review. The overall survival period ranges from 12 to 84 months. The survival distributions for mutation and state of the disease (chronic or blastic) were not statistically significantly different, X2= 3.204, p = 0.073. Conclusion: There is inconsistency in the demographic and overall survival pattern of chronic myeloid leukaemia in our environment. Further study is needed to identify the factors which can help to improve the overall survival pattern in our environment

Three-way Complex Variant Translocation Involving Long Arm of Chromosome 1 in a Chronic Myeloid Leukemia Patient

Clinical presentation of chronic myeloid leukemia (CML) with classic translocation is similar to those with variant translocations. However, the disease course, outcome and prognosis differsto a large extent. Therefore, it is important to identify and report variant cytogenetic findings. The case is being reported to improve awareness regarding such cases. Case Presentation: Herein we present a case study of 55-year-old male who presented with abdominal pain and fever. The initial complete blood count showed hyperleukocytosis with features suggestive of chronic myeloproliferative leukemia (CML). Bone marrow biopsy and cytogenetic studies were performed for confirmation. Cytogenetic analysis showed presence of complex, three-way (1;9;22)(q12;q34;q11.2) translocation involving chromosomes 1, 9 and 22. The Fluorescencein situhybridization (FISH) studies further confirmed BCR-ABL fusion gene and its atypical pattern was in concordance with aberrations observed in karyotype. The variant translocation we reported herein is unique and rarely reported in literature Discussion:We presented a complex variant case of three-way translocation with characteristic hematological and immunophenotypic findings of CML in chronic phase. To the best of our knowledge, only few cases have been documented so far involving such complex translocation. The initial response to cytoreduction was encouraging while imatinib response has to be followed in present case.Conclusion: It is important to highlight the variant translocations since such findings may influence the disease course hence play a significant role to predict outcome.

Design, synthesis, and biological evaluation of Bcr-Abl PROTACs to overcome T315I mutation

Bcr-Abl threonine 315 to isoleucine 315 (T315I) gatekeeper mutation induced drug resistance remains an unmet clinical challenge for the treatment of chronic myeloid leukemia (CML). Chemical degradation of Bcr-Abl

Expression of B7-H6 in peripheral blood and bone marrow of patient with chronic myeloid leukemia and its clinical significance / 中国输血杂志

【Objective】 To investigate the expression level of B7-H6 in peripheral blood and bone marrow of patient with chronic myeloid leukemia (CML), and to analyze its association with clinicopathological characteristics and prognosis. 【Methods】 A total of 120 CML patients from January 2010 to May 2013 were selected as study subjects. The expression of B7-H6 mRNA in CML peripheral blood and bone marrow pre- and 3-, 6-, 12-month-posttreatment was detected by quantitative real time PCR, and its correlation between prognosis and clinicopathological factors was analyzed. 【Results】 The expression level of B7-H6 mRNA in the PB, BMMCs of CML patients was lower than that of the normal population (P0.1%(P<0.0001) or without CCR (P<0.001). The expression level of B7-H6 in BMMCs was negatively correlated with the BCR-ABL1/ABL level (r=–0.260, P<0.05). Signifiant difference in PFS was observed between patients with high expression level of B7-H6 (not reached, HR: 0.06, 95% CI =0.03-0.37) and low expression level (81 months, HR: 15.58, 95% CI =2.68-30.23) in BM (P<0.05). 【Conclusion】 The low expression of the B7-H6 gene in CML is correlated with BCR-ABL1 copy number and responsiveness to treatment, and monitoring of B7-H6 expression may be used to evaluate CML prognosis, progression and treatment efficacy.

Targeting RAS phosphorylation in cancer therapy: Mechanisms and modulators

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

Uncontrolled per rectal bleeding in chronic myeloid leukaemia: a mere coincidence or a dangerous sign report of an unusual case

Bleeding haemorrhoids present commonly to surgical outpatient departments (OPDs) and sometimes in emergency. Most often conservative management suffices but infrequently the patients can land up in emergency operation theatre for uncontrolled bleeding. Some haematological disorders can also present with rectal bleeding and amongst them Chronic myeloid leukaemia (CML), a haematological malignancy, presenting as bleeding per rectum has been not been reported so far, though instances of CML with gingival bleed, epistaxis have been reported. CML per se is known to be asymptomatic (40% cases) and bleeding is rarely seen. Here we present an interesting case of an emergency hemorrhoidal bleed that was subsequently diagnosed as CML. The patient after failed conservative management for bleeding haemorrhoids was taken up for emergency haemorrhoidectomy and again a relook under general anaesthesia in the post-operative period as he continued to ooze. The total leucocyte counts which were initially high continued to rise further and the bone marrow examination was reported as chronic myeloproliferative neoplasm and the excised mass was consistent with haemorrhoids. Rectal bleeding associated with CML is so far unreported even though bleeding is seen due to platelet dysfunction from gums and nose in chronic phases of the disease. A high index of suspicion is needed particularly with deranged haematological parameters for considering a diagnosis of these rare presentations. and anaesthesia.

Clinical implications of conventional cytogenetics, fluorescence in situ hybridization (FISH) and molecular testing in chronic myeloid leukaemia patients in the tyrosine kinase inhibitor era – A review

@#Chronic myeloid leukaemia (CML) provides an illustrative disease model for both molecular pathogenesis of cancer and rational drug therapy. Imatinib mesylate (IM), a BCR-ABL1 targeted tyrosine kinase inhibitor (TKI) drug, is the first line gold standard drug for CML treatment. Conventional cytogenetic analysis (CCA) can identify the standard and variant Philadelphia (Ph) chromosome, and any additional complex chromosome abnormalities at diagnosis as well as during treatment course. Fluorescence in situ hybridization (FISH) is especially important for cells of CML patients with inadequate or inferior quality metaphases or those with variant Ph translocations. CCA in conjunction with FISH can serve as powerful tools in all phases of CML including the diagnosis, prognosis, risk stratification and monitoring of cytogenetic responses to treatment. Molecular techniques such as reverse transcriptase-polymerase chain reaction (RT-PCR) is used for the detection of BCR-ABL1 transcripts at diagnosis whereas quantitative reverse transcriptase-polymerase chain reaction (qRTPCR) is used at the time of diagnosis as well as during TKI therapy for the quantitation of BCR-ABL1 transcripts to evaluate the molecular response and minimal residual disease (MRD). Despite the excellent treatment results obtained after the introduction of TKI drugs, especially Imatinib mesylate (IM), resistance to TKIs develops in approximately 35% - 40% of CML patients on TKI therapy. Since point mutations in BCR-ABL1 are a common cause of IM resistance, mutation analysis is important in IM resistant patients. Mutations are reliably detected by nested PCR amplification of the translocated ABL1 kinase domain followed by direct sequencing of the entire amplified kinase domain. The objective of this review is to highlight the importance of regular and timely CCA, FISH analysis and molecular testing in the diagnosis, prognosis, assessment of therapeutic efficacy, evaluation of MRD and in the detection of BCR-ABL1 kinase mutations which cause therapeutic resistance in adult CML patients.

A Study On Etiology And Clinical Profile Of Patients With Thrombocytopenia

BACKGROUND: Thrombocytopenia refers to a reduction in platelet count below 1.5 lakh/microliter. The presence of thrombocytopenia in a hemogram should alert the physician to identify the underlying etiology for the prompt management of the patient. Timely identification and treatment prevent bleeding manifestations, requirement of platelet transfusions/steroids and overall impact on mortality of the patients. AIM OFSTUDY:Analysis to study the etiology, bleeding manifestation, percentage of patients requiring platelet transfusion, length of hospital stay in patients with thrombocytopenia. METHODOLOGY: 100 cases thrombocytopenia both male and female were included in the study. The diagnosis was made on peripheral smear and Hemogram. RESULTS: Dengue fever was the most common cause of thrombocytopenia with 43 cases. Sepsis with 23 cases was the second commonest. Bleeding manifestations were seen in 23% of the study population.100% of the patients with platelet count less than 10,000/microlitre had bleeding manifestations. 26 patients (26%) received platelet transfusion out of which 23 were therapeutic and 3 were prophylactic transfusions. Steroid therapy was given in 11% of patients. Mortality was highest in patients with sepsis induced thrombocytopenia. CONCLUSION:This study shows that Dengue fever is the commonest diagnosis made in patients who are detected to have thrombocytopenia. One fifth of patients with platelet count less than 1,00,000/microlitre tend to have bleeding manifestation, commonest being GI bleed, petechial rash and epistaxis. Majority of the bleeding occurs with platelet count less than 10,000. The proportion of patients receiving therapeutic platelet transfusion was higher compared to prophylactic transfusion.

Does BCR-ABL transcript type influence the prognosis of patients in chronic myelogenous leukemia chronic phase?

ABSTRACT Introduction and objective: In this study, we evaluated the influence of the transcript type on hematological and clinical parameters, as well as the event-free survival of 50 patients in the Chronic myeloid leukemia chronic phase. Methods: We reviewed the medical records of 55 patients with Chronic myeloid leukemia. The eligibility criteria were based on the availability of hematological and clinical baseline data in the medical records. Data on BCR-ABL transcripts were obtained from medical records. Results: Eighteen patients (36%) had the b2a2 transcript, 24 (48%) had b3a2 and 8 (16%) had b2a2/b3a2. The median platelet count for transcripts b2a2, b3a2 and b2a2/b3a2 was 320.65 × 103/L, 396 × 103/L, and 327.05 × 103/L, respectively (p = 0.896). We could not find any differences in relation to the other hematological parameters, when compared to the transcript type. Comparison between spleen and liver size and type of transcript did not differ inside the groups (p = 0.395 and p = 0.647, respectively) and the association between risk scores and transcript type did not show statistical significance (p > 0.05). The 21-month probability for event-free survival was 21%, 48% and 66% for the transcripts b2a2, b3a2 and b2a2/b3a2 respectively (p = 0.226) Conclusion: We conclude that the expression BCR-ABL transcripts have no influence on hematological, clinical and event-free survival parameters of patients in the Chronic myeloid leukemia chronic phase.

Imatinib induced bone marrow hypoplasia in a case of chronic myelogenous leukemia

Imatinib mesylate a tyrosine kinase inhibitor first introduced for the treatment of chronic myelogenous leukaemia (CML) since May 2001, has revolutionised the management of CML. Imatinib is the first choice of treatment for patient with CML chronic phase (CML-CP) and generally the drug is well tolerated. A number of haematological and non-haematological side effects are associated with it. Bone marrow hypoplasia is one of the rare side effects noted with imatinib. We report a case of 46-year-old male a case of CML-CP who developed bone marrow hypoplasia following treatment with imatinib for a period of six months with bone marrow biopsy showing decreased cellularity.

Effects of miR-221 on cell proliferation and apoptosis of chronic myeloid leukemia K562 cells and its mechanism / 中国肿瘤生物治疗杂志

@# Objective: To investigate the effect of down-regulation of miR-221 on cell proliferation and apoptosis of chronic myeloid leukemia (CML) K562 cells and its related regulatory mechanism. Methods: K562 cells were divided into control group, miRNAnegative control (miR-NC) group, miR-221 inhibitor group, miR-221 inhibitor+ negative control siRNA(NC siRNA) group and miR-221 inhibitor+SOCS3 siRNA group. The cells in the control group received no additional treatment. Cells in miR-NC group and miR-221 inhibitor group were transfected with miR-NC and miR-221 inhibitor, respectively. Cells in miR-221 inhibitor+NC siRNA group and miR-221 inhibitor+SOCS3 siRNA group were transfected with NC siRNA and SOCS3 siRNA, respectively, on the basis of successful transfection with miR-221 inhibitor. The transfection efficiency of miR-221 inhibitor was identified by qPCR. Cell viability in each group was measured by CCK-8 assay. Apoptosis in each group was detected by Annexin V-FITC/PI staining using a flow cytometry. The protein expressions of SOCS3, p-JAK1, p-JAK2, p-STAT3 and survivin in each group were detected by WB. Results: Compared with the control group, miR-221 expression was significantly down-regulated in miR-221 inhibitor group (P<0.01), cell viability was significantly reduced at 48 and 72 h after transfection (P<0.05 or P<0.01), the number of apoptotic cells was significantly increased (P< 0.01), the expression of SOCS3 was significantly increased (P<0.01) and the expression levels of p-JAK1, p-JAK2, p-STAT3 and survivin were significantly reduced (all P<0.01). Compared with miR-221 inhibitor group, cell viability was significantly increased at 24, 48 and 72 h after transfection (P<0.05 or P<0.01), the number of apoptotic cells was significantly decreased (P<0.01) and the expression levels of p-JAK1, p-JAK2, p-STAT3 and survivin were significantly increased in miR-221 inhibitor+SOCS3 siRNA group (all P< 0.01). Conclusion: Down-regulation of miR-221 inhibits proliferation and promotes apoptosis of K562 cells, the mechanism of which may be related with up-regulating SOCS3 expression to suppress JAK-STAT3 signaling pathway.

Significance of alternative splicing in drug resistance of chronic myeloid leukemia / 中国肿瘤临床

Alternative splicing (AS) is a process by which the transcriptome diversity, and thereby the proteome diversity, is augment-ed by splicing or joining together different parts of the pre-mRNA in eukaryotic cells . AS at different splice sites is regulated by multi-ple cis-acting elements and trans-acting factors. Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease in which there is a translocation between the long arms of chromosome 9 and chromosome 22, represented as t(9;22) (q34;q11). This translocation results in the formation of a BCR-ABL fusion gene. Hence it is not surprising that resistance to tyrosine kinase inhibitors, which inhibit BCR-ABL activity, has become a critical problem in the clinical treatment of CML. Using second generation high-throughput sequencing technology, it has been found that AS abnormalities are closely related to the occurrence, progression, drug resistance, and immune escape of CML. This paper reviews the research related to AS and CML resistance and investigates the potential causes of CML resis-tance. Drug resistance mechanisms and potential therapeutic targets are also reviewed.

Four-year follow-up of patients with imatinib-resistant or intolerant chronic myeloid leukemia receiving dasatinib: efficacy and safety / 医学前沿

Dasatinib is a highly effective second-generation tyrosine kinase inhibitor used to treat chronic myeloid leukemia (CML). In 2007, a pivotal phase-2 study of dasatinib as second-line treatment was initiated in 140 Chinese CML patients. This report from the 4-year follow-up revealed that 73% of 59 patients in chronic phase (CML-CP) and 32% of 25 patients in accelerated phase (CML-AP) remained under treatment. The initial dosage of dasatinib for CML-CP and CML-AP patients were 100 mg once daily and 70 mg twice daily (total = 140 mg/ day), respectively. The cumulative major cytogenetic response (MCyR) rate among patients with CML-CP was 66.1% (versus 50.8% at 18 months), and the median time to MCyR was 12.7 weeks. All CML-CP patients who achieved MCyR after a 4-year follow-up also achieved a complete cytogenetic response. The cumulative complete hematological response (CHR) rate among patients with CML-AP was 64% (16/25), with three CML-AP patients achieving CHR between 18 months and 4 years of follow-up; the median time to CHR was 16.4 weeks. The adverse event (AE) profile of dasatinib at 4 years was similar to that at 6 and 18 months. The most frequently reported AEs (any grade) included pleural effusion, headache, and myelosuppression. These long-term follow-up data continue to support dasatinib as a second-line treatment for Chinese patients with CML.

The JAK2 V617F Mutation in Chronic Myeloid Leukaemia within a BCR-ABL Positive Cohort of Beninese Patients

Chronic myelogenous leukaemia (CML) is an acquired myeloproliferative disorder (MPD) characterized by a chromosomal abnormality (the Philadelphia chromosome) that causes the chimeric BCR-ABL oncogene. An acquired genetic mutation in exon 12 of the JAK2 tyrosine kinase gene leading to a substitution of a valine for a phenylalanine (V617F) has been described as the most common form of CML for those who test negative for the Philadelphia (Ph) chromosome. According to World Health Organization (WHO) classifications (2008), the JAK2 V617F mutation and the BCR-ABL translocation are mutually exclusive for Ph(-) and Ph (+) MP, respectively. We studied the JAK2 V617F mutation in Ph+ myeloid leukaemia in a cohort of 27 Beninese patients. The ARMS multiplex PCR technique was used to identify the JAK2 V617F mutation in all patients. Most of the patients were diagnosed as in the chronic phase (88.9%) of the disease, and all of them were carriers of the Philadelphia chromosome and considered Ph (+). No patients with the BCR/ABL translocation carried the JAK2 V617F mutation. JAK2 V617F is specific to Philadelphia gene negative MP.

The effect of drug transporter gene polymorphisms on susceptibility to imatinib in chronic myelogenous leukemia / 中国肿瘤临床

As a first generation tyrosine kinase inhibitor, imatinib is the gold standard drug for the clinical treatment of chronic myelog-enous leukemia. However, interindividual differences in resistance and response to imatinib have been widely observed. In vivo and in vitro studies have confirmed that ATP-binding cassette transporters, organic cation transporters, and organic anion transporting poly-peptides have a large effect on imatinib pharmacokinetics and pharmacodynamics. In addition, the gene polymorphisms of drug trans-porters can directly or indirectly influence the intracellular concentration of imatinib, resulting in differences in treatment efficacy among chronic myelogenous leukemia patients. This review profiles the effect of drug transporter gene polymorphisms on susceptibili-ty to imatinib in chronic myelogenous leukemia so as to provide reference to further clinical researches.

Standard of care of patients with Chronic Myeloid Leukemia (CML) treated in community based oncology group practices between 2001-2015 in Rhineland- Palatinate (Germany)

Background: The aim of this study was to assess retrospectively treatment and outcome of CML-patients in community based oncology practices in Germany and whether European LeukemiaNET (ELN) recommendations were followed. Method: All Ph+, BCR-ABL1+ CML-patients who were treated between 11/2001 and 12/2015 in nine oncology group practices were analyzed retrospectively. Results: Two hundred sixty patients with a median age of 60 (18­90) were analyzed. 254 (98%) were in chronic phase, 5 (2%) in accelerated and 1 (0.4%) in blast crisis. 248 patients (95%) received some form of TKI-therapy. 1st line TKI was imatinib in 197 patients (79%), 51 (21%) received a second generation TKI. 75% of TKI-therapies were monitored by PCR. Overall survival after 10 years according to Charlson comorbidity index (CCI) was: CCI 2: 100%; CCI 3­4: 83%; CCI 5­6: 52%; CCI ≥7: 39%. More patients died from comorbidities (8%) than from CML (5%). Whether patients died was strongly correlated to CCI at diagnosis: CCI 2: 3% of patients died, CCI 3­4: 16% of patients died, CCI 5­6: 38% of patients died, CCI ≥ 7: 42% of patients died. Conclusion: CML-patients treated in oncology group practices receive standard of care as recommended by ELN. Overall survival in routine care is comparable to international studies. Molecular monitoring should be improved (AU)

The role of aptamer-siRNA nucleic acid compound in promoting the apoptosis of K562 cells / 西安交通大学学报(医学版)

Objective To observe the effect of aptamer-siRNA nucleic acid compound on the apoptosis of K562 cells in human chronic myelogenous leukemia (CML)and explore its acting mechanisms.Methods K562 cells were transfected with different concentrations of aptamer-siRNA solution.The effects of aptamer-siRNA on the proliferation and apoptosis of K562 cells were detected by MTT method and AnnexinV/PI double staining method,respectively.The effects of aptamer-siRNA on the expressions of bcl-2,Bax and casepase-3 at protein and mRNA levels in K562 cells were detected by Western blot and RT-PCR method,respectively.Results Compared with the control group,the proliferation of K562 cells was significantly inhibited,early apoptosis rate of K562 cells increased significantly,the expression levels of bcl-2 protein and mRNA were significantly decreased,while the expression levels of Bax and caspase-3 protein and mRNA were significantly increased after transfection with aptamer-siRNA (P <0.05).Aptamer-siRNA nucleic acid complex at the concentration of 50 -250 μmol/L)had a significant dose-effect relationship on bcl-2,Bax and caspase-3 mRNA.Conclusion Aptamer-siRNA nucleic acid compound can promote the decreased number of bcl-2 gene and the growth of Bax and caspase-3 genes,thus promoting the apoptosis of K562 cells.