scholarly journals Tasigna Induced Musculoskeletal Disorder pada Pasien Chronic Myeloid Leukemia

2019 ◽  
Vol 8 (1) ◽  
pp. 21
Author(s):  
Indah Sapta Wardani
Keyword(s):  
Targeted Therapy ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Musculoskeletal Disorder ◽  
Kinase Inhibitor

Chronic myeloid lekemia (CML) merupakan salah satu jenis leukemia yang banyak dijumpai pada usia dewasa. Tasigna (Nilotinib) merupakan salah satu pengobatan yang digunakan sebagai target terapi pada CML. Efek samping Tasigna jarang ditemui dan sampai saat ini patogenesisnya belum jelas. Dalam naskah ini dilaporkan sebuah kasus seorang laki-laki 34 tahun yang telah tegak dengan CML fase kronis berdasarkan pemeriksaan sitogenetik dengan BCR-ABL Ph+ dan mendapat targeted therapy Tasigna yang merupakan suatu multiprotein kinase inhibitor dengan target menghambat autofosforilasi BCR-ABL, dengan dosis 2x300 mg. Dalam perjalanannya pasien mengalami suatu efek samping terapi yang bermanifestasi berupa perdarahan yang disebabkan oleh trombositopenia yang diinduksi oleh Tasigna dan manifestasi muskuloskeletal yang kemungkinan disebabkan oleh gangguan keseimbangan elektrolit dan mineral, yang membaik dengan penundaan pemberian Tasigna selama perawatan. Tata laksana pasien dilakukan penghentian pemberian Tasigna dan diberikan terapi suportif. Pemberian kembali Tasigna dipertimbangkan apabila efek samping yang ada telah hilang. Bila efek samping menetap, berat, atau muncul pada pemberian ulang, dianggap pasien tersebut tidak toleran terhadap Tasigna dan harus diganti dengan agen target terapi yang lain.

scholarly journals CHRONIC MYELOID LEUKEMIA IN PATIENT WITH THE KLINEFELTER SYNDROME

2016 ◽  
Vol 38 (3) ◽  
pp. 195-197 ◽  
Author(s):  
S V Andreieva ◽  
K V Korets ◽  
O A Kyselova ◽  
O E Ruzhinska ◽  
I M Serbin
Keyword(s):  
Targeted Therapy ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Chromosomal Abnormality ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Klinefelter Syndrome ◽  
Abl Tyrosine Kinase ◽  
Abl Tyrosine Kinase Inhibitor

Aim: Genetic inborn along with acquired diseases arise due to the lesions in genome of multipotent hematopoietic stem cells. The aim was to study an influence of constitutional anomaly, Klinefelter syndrome, and additional structural rearrangements on the BCR-ABL tyrosine kinase inhibitor targeted therapy efficacy. Material and Methods: We describe a 32-year-old male patient with chronic myeloid leukemia (CML) who was detected to have sex chromosomal abnormality during evaluation for Philadelphia chromosome. Results: At diagnosis of CML, two clones were detected by standard cytogenetic investigation of bone marrow cells: 1) clone with translocation t(9;22)(q34;q11), with two sex X chromosomes and absence sex chromosome Y; 2) clone with t(9;22) and unbalanced t(Y;20)(q11;q13). Analysis of blast transformed lymphocytes from peripheral blood showed karyotype 47,XXY. Monitoring of targeted therapy with second generation inhibitor of BCR-ABL tyrosine kinase indicated a cytogenetic remission and absence of BCR-ABL1 fusion signals after 11 months. Conclusions: Absence of translocation t(9;22)(q34;q11) in blast transformed T-lymphocytes at diagnosis of CML evidences that this translocation may appear not only at the level of multipotent haemopoietic cell progenitors but also may have oligo lineage myeloid origin. Presence of additional structural chromosomal abnormality in the clone with t(9;22)(q34;q11) does not affect the efficacy of therapy with the use of second generation BCR-ABL tyrosine kinase inhibitor.

Treatment of Chronic Myeloid Leukemia Elderly Patients in the Tyrosine Kinase Inhibitor Era

2013 ◽  
Vol 13 (7) ◽  
pp. 755-767 ◽  
Author(s):  
Domenico Russo ◽  
Michele Malagola ◽  
Cristina Skert ◽  
Carla Filì ◽  
Cesare Bergonzi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Elderly Patients ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor

scholarly journals Thrombotic microangiopathy in dasatinib-treated patients with chronic myeloid leukemia

2019 ◽  
Vol 4 (1-2) ◽  
pp. 41-45 ◽  
Author(s):  
Takeo Koshida ◽  
Sylvia Wu ◽  
Hitoshi Suzuki ◽  
Rimda Wanchoo ◽  
Vanesa Bijol ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitor ◽  
Tyrosine Kinase Inhibitors ◽  
Thrombotic Microangiopathy ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Kidney Biopsy ◽  
Kinase Inhibitor ◽  
Target Effect

Dasatinib is the second-generation tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia. Proteinuria has been reported with this agent. We describe two kidney biopsy–proven cases of dasatinib-induced thrombotic microangiopathy that responded to stoppage of dasatinib and using an alternate tyrosine kinase inhibitor. Certain specific tyrosine kinase inhibitors lead to endothelial injury and renal-limited thrombotic microangiopathy. Hematologists and nephrologists need to be familiar with this off-target effect of dasatinib.

scholarly journals Potential treatment for chronic myeloid leukemia using microRNA: in silico comparison between plants and human microRNAs in targeting BCR-ABL1 gene

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Syarifah Faezah Syed Mohamad ◽  
Marjanu Hikmah Elias
Keyword(s):  
Targeted Therapy ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinase ◽  
Pathway Analysis ◽  
Protein Interaction ◽  
Protein Interaction Network ◽  
In Silico ◽  
Myeloid Leukemia ◽  
Interaction Network ◽  
Folding Energy

Abstract Background Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the expression of the BCR-ABL1 fusion gene. Tyrosine kinase inhibitors (TKI) are used to treat CML, but mutations in the tyrosine kinase domain contribute to CML chemo-resistance. Therefore, finding alternative molecular-targeted therapy is important for the comprehensive treatment of CML. MicroRNAs (miRNA) are small non-coding regulatory RNAs which suppress the expression of their target genes by binding to the 3′ untranslated region (3′UTR) of the target mRNA. Hypothetically, the miRNA-mRNA interaction would suppress BCR-ABL1 expression and consequently reduce and inhibit CML cell proliferation. Thus, our objective was to determine the target interaction of human and plant miRNAs targeting the 3′UTR region of BCR-ABL1 in terms of miRNA binding conformity, protein interaction network, and pathways using in silico analysis. The 3′UTR sequence of BCR-ABL1 is obtained from Ensembl Genome Browser while the binding conformity was determined using the PsRNATarget Analysis Server, RNA22, Target Rank Server, and DIANA TOOLS. Protein-protein interaction network and pathway analysis are determined using STRING, Cytoscape, and KEGG pathway analysis. Results Five plants and five human miRNAs show strong binding conformity with 3′UTR of BCR-ABL1. The strongest binding conformity was shown by Oryza sativa’s Osa-miR1858a and osa-miR1858b with −24.4 kcal/mol folding energy and a p value of 0.0077. Meanwhile, in human miRNA, the hsa-miR-891a-3p shows the highest miTG score of 0.99 with −12 kcal/mol folding energy and a p value of 0.037. Apart from ABL1, osa-miR1858a/osa-miR1858b and hsa-miR891a-3p also target other 720 and 645 genes, respectively. The interaction network of Osa-miR1858a/osa-miR1858b and hsa-miR891a-3p identifies nineteen and twelve ABL1’s immediate neighboring proteins, respectively. The pathways analysis focuses on the RAS, MAPK, CML, and hematopoietic cell lineage pathway. Conclusion Both plant and human miRNAs tested in this study could be a potential therapeutic prospect in CML treatment, but thermodynamically, osa-miR1858a/osa-miR1858b binding to ABL1 is more favorable. However, it is important to carry out more research in vitro and in vivo and clinical studies to assess its efficacy as a targeted therapy for CML. Graphical abstract

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