scholarly journals The Association of Glutathione S-Transferase P1 Polymorphism to Imatinib Mesylate Resistance in Chronic Myelogenous Leukemia Patients According to Haematology Response at General Hospital Haji Adam Malik and Branch Hospital in Kota Medan

2021 ◽  
Vol 8 (9) ◽  
pp. 551-557
Author(s):  
Ainun Basyiroh Lubis ◽  
Dairion Gatot ◽  
Savita Handayani
Keyword(s):  
General Hospital ◽  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Response To Treatment ◽  
P Value ◽  
Research Subjects ◽  
Imatinib Resistance ◽  
Exact Test ◽  
Metabolism Enzymes

Objective: Variations in the genes coding for drug metabolism enzymes may explain the variability response to treatment. Previous studies reported that GSTP1 polymorphism was associated with the incidence of Imatinib Mesylate resistance as first-line therapy in CML patients. This study aims to determine the association between GSTP1 polymorphism and Imatinib Mesylate resistance in CML patients according to haematology response. Methods: Total of 46 people (consisting of 23 CML patients with Imatinib Mesilat resistance and 23 CML patients without Imatinib Mesilat resistance) at General Hospital H. Adam Malik and branch hospital in Medan City, Indonesia was analyzed in this study. Blood samples were taken for examination of GSTP1 polymorphism through Polymerase Chain Reaction (PCR). Resistance status was taken from medical records based on ELN criteria. Data were analyzed using Fisher's Exact test; p value <0,05 was applied to each statistical test as significant. Result: The distribution of research subjects characteristic was divided into imatinib resistance and non-imatinib resistance groups. In both cases, the highest frequency was found in male (65,2% and 69,6%) in 35-44 years old group (34,8% and 39,1%). In the imatinib resistance group, the highest frequency was found in Javanese (39,1%) and GSTP1 polymorphism Ile/Ile (65,2%). In the non-imatinib-resistant group, the highest frequency was found in Batak tribe (43,5%) and GSTP1 polymorphism Ile/Val (52,2%). This study found 11 cases of leukocytosis and 7 cases of thrombocytosis in the imatinib resistance group. According to statistical measurement, p value was 0,142 (p>0,05). Conclusion: The association of GSTP1 polymorphism to imatinib mesylate resistance in chronic myelogenous leukemia patients according to haematology response was not significant. Keywords: Chronic Myeloid Leukemia, GSTP1 Polymorphism, Imatinib Mesylate Resistance.

Relationship between Clinical/Hematological Response and Increase of Plamacells in the Bone Marrow of Patients with Chronic Myelogenous Leukemia Imatinib Mesylate Treatment (631).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4552-4552
Author(s):  
Alessandro Poggi ◽  
Ivana Pierri ◽  
Silvia Catellani ◽  
Francesca Olcese ◽  
Antonella Marasco ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Tyrosine Kinase ◽  
Imatinib Mesylate ◽  
B Lymphocytes ◽  
Chronic Myelogenous Leukemia ◽  
Peripheral Blood ◽  
Kinase Inhibitor ◽  
Myelogenous Leukemia ◽  
Response To Treatment ◽  
Imatinib Treatment

Abstract Tyrosine kinase inhibitors, such as imatinib mesylate (Gleevec, Novartis, formerly known as STI571) are the first line treatment of Chronic Myelogenous Leukemia (CML) and of a rare form of gastroenteric stromal cancer. It has been recently reported that in the latter case, tumor cells are refractory to imatinib antiproliferative effect in vitro and the response to the drug in vivo is due to immunocompetent cells, able to produce cytokines with antineoplastic activity. In this study, 20 CML patients, prior and during treatment with imatinib mesylate, underwent bone marrow (BM) aspirates every 6 months, including: morphologic and phenotypic analysis, cytogenetic and biomolecular evaluation, compared to peripheral blood. Plasma from BM and peripheral blood was also recovered for cytokyne-chemokine dosage. We report that in 12 out of 20 CML patients a significant increase in the percentage of BM lymphoplasmocytoid cells was observed upon treatment with imatinib mesylate, with >10% (range 10–16%) of CD20+CD126+cells. Among this population, two third of cells coexpressed IgM and one third was IgD+, while a smaller fraction of IgM+CD126+CD20– (3–4%) or IgD+CD126+CD20- (2–3%) cells was also found. The lasting 8 patients had<5% of CD20 +CD126+ lymphocytes (range2–4%), 2/3 coexpressing IgM and 1/3 coexpressing IgD. All patients with increased number of CD126+ B lymphocytes underwent hematologic remission, 7 of them with complete molecular and cytogenetic remission. On the other hand, among the patients with low or undetectable CD20+CD126+cells, only 4 underwent hemathological remission and none of them displayed stable cytogenetyc and molecular remission. In two patients relapsed after six months of treatment, the fraction of BM CD20+CD126+ lymphocytes decreased from 16% and 11% to 7 and 5%, respectively, with undetectable IgM+ CD126+CD20- or IgD+ CD126+CD20- cells. These data suggest that this population of lymphoplasmocytoid B cells depends on or contribute to the pharmacological response; by the way, this phenomenon might help in monitoring the outcome of disease and the response to treatment. To check this item and understand the biochemical mechanisms substaining the observed increase in BM lymphoplasmocitoid cells on imatinib treatment, we wonder if the production of cytokines able to induce B lymphocytes differentiation, such as interleukin (IL)-4, IL-6 (whose receptor is CD126), IL-3, IL10 or IL-21 was affected by imatinib administration. To this aim, both soluble cytokines (by ELISPOT) and their mRNA (by real time polymerase chain reaction) were evaluated in the BM of these patients: moreover, the expression of MCP-1, SDF-1, IP-10 and IL-8 were also measured, to verify whether the increse in BM CD20+ CD126+ lymphocytes was due to a redistribution rather than to “in situ” differentiation. Preliminary results seem to indicate that the latter hypothesis is unlikely; in addition, when CD20+ CD126+ were increased in the BM, they also raised in the peripheral blood. These immunological events might have a role in the response to tyrosine kinase inhibitor and need further investigations.

Detection of BCR-ABL kinase mutations in CD34+ cells from chronic myelogenous leukemia patients in complete cytogenetic remission on imatinib mesylate treatment

Blood ◽  
2005 ◽  
Vol 105 (5) ◽  
pp. 2093-2098 ◽  
Author(s):  
Su Chu ◽  
Helen Xu ◽  
Neil P. Shah ◽  
David S. Snyder ◽  
Stephen J. Forman ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Drug Binding ◽  
Myelogenous Leukemia ◽  
In Vitro Mutagenesis ◽  
Mrna Levels ◽  
Imatinib Resistance ◽  
Secondary Resistance ◽  
Abl Kinase ◽  
Cd34 Cells

AbstractThe BCR-ABL kinase inhibitor imatinib mesylate induces complete cytogenetic response (CCR) in a high proportion of chronic myelogenous leukemia (CML) patients. However, patients in CCR usually demonstrate evidence of residual BCR-ABL–positive progenitors. The mechanisms underlying persistence of small numbers of malignant progenitors in imatinib-sensitive patients are unclear. BCR-ABL kinase domain mutations affecting drug binding can lead to secondary resistance to imatinib. We show here that kinase mutations could be detected in CD34+ cells isolated from CML patients in CCR on imatinib. Most mutations seen have not been reported in previous clinical studies. Interestingly, several of the involved amino acid positions have been implicated in an in vitro mutagenesis screen. These BCR-ABL mutations were associated with varying levels of imatinib resistance. Two of 5 patients in whom mutations were detected on initial evaluation have relapsed. In addition, 4 patients in whom mutations were not initially detected, but with rising BCR-ABL mRNA levels on quantitative polymerase chain reaction (Q-PCR) analysis, had mutations detected on follow-up evaluation. We conclude that BCR-ABL kinase mutations can be detected in CD34+ cells from CML patients in CCR on imatinib, may contribute to persistence of small populations of malignant progenitors, and could be a potential source of relapse.

scholarly journals Potential effect of Imatinib on some sex hormones for male patients of Chronic Myelogenous Leukemia in Baghdad province

Bionatura ◽  
2021 ◽  
Vol 6 (4) ◽  
pp. 2193-2195
Author(s):  
Abeer Anwer Ahmed ◽  
Khaleed J Khaleel ◽  
Alaa Abbas Fadhel
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Sex Hormones ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
P Value ◽  
Male Patients ◽  
The Impact

Imatinib Mesylate is an oral chemotherapy drug that has been used to treat Chronic Myelogenous Leukemia (CML). It works as an inhibitor of oncogene tyrosine kinase BCR-ABLI as a target therapeutic agent. Despite the drug is well tolerated in most patients, impaired testosterone production and Gynecomastia after therapy might happen. The current study aims to evaluate the impact of Imatinib Mesylate on sex hormones of CML male patients in Baghdad province. Blood specimens were collected from (42) CML patients aged 23 to 68 years who used Imatinib drug for more than two years, and (45) normal persons aged 25 to 65 years as a control group. Exclusion criteria were performed for both control and CML patient's groups, including people with diabetes, hypertensive, and males complaining of infertility after taking medical history for every participant. The blood level of hemoglobin (Hb), white blood cells (WBC), platelet count, testosterone, LH, and FSH were evaluated and investigated. The obtained results showed a significantly lower level of testosterone (2.73+- 0.97) ng/mL than the control group (4.72 ±1.02) ng/mL with a p-value of 0.000. While LH (4.53±2.1) mIU/mL and FSH (5.12 ± 2.83) mIU/mL were significantly higher than the control group (3.77± 0.8) mIU/mL and (3.85±0.807) mIU/mL with p-value of 0.026 and 0.005 respectively. Moreover, the outcomes revealed a moderate positive correlation (r = +0.348) between LH hormone levels with a duration increasing time of using Imatinib, while platelet showed a moderate negative correlation (r = -0.321) with time-consuming using that drug. In conclusion, Imatinib might harm testis functions and some hematological parameters that could increase using this drug.

Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3547-3553 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge Cortes ◽  
Susan O'Brien ◽  
Francis J. Giles ◽  
Maher Albitar ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Response Rate ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Blast Phase ◽  
Molecular Abnormalities ◽  
Philadelphia Chromosome Positive

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor [Ph+, 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P = .001), longer median survival (7 versus 4 months, P = .04), and lower 4-week induction mortality (4% versus 15%, P = .07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

Several Bcr-Abl kinase domain mutants associated with imatinib mesylate resistance remain sensitive to imatinib

Blood ◽  
2003 ◽  
Vol 101 (11) ◽  
pp. 4611-4614 ◽  
Author(s):  
Amie S. Corbin ◽  
Paul La Rosée ◽  
Eric P. Stoffregen ◽  
Brian J. Druker ◽  
Michael W. Deininger
Keyword(s):  
Imatinib Mesylate ◽  
Kinase Inhibitor ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Kinase Domain ◽  
Myelogenous Leukemia ◽  
Imatinib Resistance ◽  
Abl Kinase ◽  
Cellular Assays ◽  
Kinase Domain Mutations

Abstract Imatinib mesylate is a selective Bcr-Abl kinase inhibitor, effective in the treatment of chronic myelogenous leukemia. Most patients in chronic phase maintain durable responses; however, many in blast crisis fail to respond, or relapse quickly. Kinase domain mutations are the most commonly identified mechanism associated with relapse. Many of these mutations decrease the sensitivity of the Abl kinase to imatinib, thus accounting for resistance to imatinib. The role of other mutations in the emergence of resistance has not been established. Using biochemical and cellular assays, we analyzed the sensitivity of several mutants (Met244Val, Phe311Leu, Phe317Leu, Glu355Gly, Phe359Val, Val379Ile, Leu387Met, and His396Pro/Arg) to imatinib mesylate to better understand their role in mediating resistance.While some Abl mutations lead to imatinib resistance, many others are significantly, and some fully, inhibited. This study highlights the need for biochemical and biologic characterization, before a resistant phenotype can be ascribed to a mutant.

Interleukin 11 May improve thrombocytopenia associated with Imatinib mesylate therapy in chronic Myelogenous leukemia

2004 ◽  
Vol 28 (6) ◽  
pp. 613-618 ◽  
Author(s):  
Patricia Ault ◽  
Hagop Kantarjian ◽  
Mary Alma Welch ◽  
Francis Giles ◽  
Mary Beth Rios ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Interleukin 11

scholarly journals Successful Treatment of Extramedullary Blast Crisis of Chronic Myelogenous Leukemia with Imatinib Mesylate (STI571)

2003 ◽  
Vol 42 (8) ◽  
pp. 740-742 ◽  
Author(s):  
Kotaro NAITO ◽  
Takehiko MORI ◽  
Keiko MIYAZAKI ◽  
Yuiko TSUKADA ◽  
Yasuo IKEDA ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Successful Treatment ◽  
Blast Crisis ◽  
Myelogenous Leukemia ◽  
Extramedullary Blast Crisis
Sign in / Sign up

Export Citation Format

Share Document