Oral melanosis after tyrosine kinase inhibition with Imatinib for chronic myelogenous leukemia: Report of a case and review of the literature

2011 ◽  
Vol 17 (5) ◽  
Author(s):  
Michelle Wong ◽  
Shachar Sade ◽  
Melanie Gilbert ◽  
Hagen B E Klieb
Keyword(s):  
Tyrosine Kinase ◽  
Chronic Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Review Of The Literature ◽  
Kinase Inhibition ◽  
Tyrosine Kinase Inhibition

A Population (Registry) Based Analysis of the Impact of Bcr-Abl Specific Tyrosine Kinase Inhibition on Survival after Diagnosis of Philadelphia Chromosome Positive Chronic Myelogenous Leukemia..

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3237-3237
Author(s):  
A. Robert Turner ◽  
Joanne D Hewitt ◽  
Anmmd Kamruzzaman ◽  
Loree M. Larratt ◽  
Deborah A. Rusnak ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Chronic Myelogenous Leukemia ◽  
Philadelphia Chromosome ◽  
Myelogenous Leukemia ◽  
Alpha Interferon ◽  
Cell Transplant ◽  
Kinase Inhibition ◽  
Tyrosine Kinase Inhibition ◽  
The Impact ◽  
Philadelphia Chromosome Positive

Abstract Specific tyrosine kinase inhibition (TKI) of the bcr-abl fusion protein in Philadelphia chromosome positive chronic myelogenous leukemia (CML) was introduced into general use in 2000 after a plenary abstract presentation to ASH in December 1999. Here we report the impact of the use of TKI on survival of all patients with CML in a total population based registry in the province of Alberta in Canada where BMT has been in use since 1980, α interferon +/− cytarabine since 1990 and TKI since 2000. All therapies have been fully funded by the public health care system in Alberta. Alberta’s population in 2000 was 2.97 million. Prior to 2000, allogeneic stem cell transplant (BMT) was the only curative therapy available but its application was limited to a minority of patients with CML. Alpha interferon induced a cytogenetic remission in some CML and alpha interferon plus cytarabine prolonged survival in CML. CML AML n 5 yr survival % BMT n 5 yr survival % BMT *59% of deaths occurred in the first year after diagnosis in the 2000–06 cohort 1980–89 303 40% NA 540 13% NA 1990–99 276 48% 25 692 15% 13 2000–06 216 83%* 8 680 25% 16 p<0.0001 p<0.0001 A 5 year survival for CML (1980–89) of 40% is consistent with published data. The 48% 5 year survival for CML (1990–99) reflects the benefit of interferon. The 5 year survival of acute myelogenous leukemia (AML) in Alberta is provided for comparison to reflect general improvement in care. The proportion of AML patients who had a BMT did not significantly change while there was a significant reduction in numbers of CML transplanted in 2000–06. Transplant status did not significantly affect outcome in CML patients with 75% of non-BMT and 84% of BMT patients still alive at 5 years (p=0.08). In contrast, transplant status was statistically significant in AML, with 5 year survival of 49% in those treated with BMT, compared to 17% of those not transplanted (p<0.0001). The results of this study show that TKI therapy (primarily imatinib) has had a major impact on the outcome of CML treatment in the province of Alberta. Long term survival, >80%, has been achieved and it appears that almost all of these patients can look forward to a normal life expectancy without the need for BMT.

scholarly journals Effects of tyrosine kinase inhibition on bone metabolism: untargeted consequences of targeted therapies

2014 ◽  
Vol 21 (3) ◽  
pp. R247-R259 ◽  
Author(s):  
José O Alemán ◽  
Azeez Farooki ◽  
Monica Girotra
Keyword(s):  
Tyrosine Kinase ◽  
Targeted Therapies ◽  
Mineral Metabolism ◽  
Myelogenous Leukemia ◽  
Cytotoxic Agents ◽  
Imatinib Treatment ◽  
Vegf Inhibitors ◽  
Kinase Inhibition ◽  
Tyrosine Kinase Inhibition ◽  
Oncologic Treatment

Tyrosine kinase inhibitors (TKIs) are at the forefront of molecular-targeted therapies for cancer. With the advent of imatinib for the treatment of chronic myelogenous leukemia, a new wave of small-molecule therapeutics redefined the oncologic treatment to become chronically administered medications with tolerable side-effect profiles compared with cytotoxic agents. Effects on bone mineral metabolism were observed during early imatinib treatment, in the form of hypophosphatemia with increased urinary phosphorus excretion. This finding led to detailed investigations of off-target effects responsible for changes in bone cell maturation, activity, and impact on bone mass. Subsequently, another BCR-Abl inhibitor (dasatinib), vascular endothelial growth factor (VEGF) inhibitors (sorafenib and sunitinib) as well as rearranged during transfection (RET) inhibitors (vandetanib and cabozantinib) were developed. Inhibition of bone resorption appears to be a class effect and is likely contributed by TKI effects on the hematopoietic and mesenchymal stem cells. As long-term, prospective, clinical outcomes data accumulate on these targeted therapies, the full extent of off-target side effects on bone health will need to be considered along with the significant benefits of tyrosine kinase inhibition in oncologic treatment.

scholarly journals Targeting USP47 overcomes tyrosine kinase inhibitor resistance and eradicates leukemia stem/progenitor cells in chronic myelogenous leukemia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hu Lei ◽  
Han-Zhang Xu ◽  
Hui-Zhuang Shan ◽  
Meng Liu ◽  
Ying Lu ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Progenitor Cells ◽  
Chronic Myelogenous Leukemia ◽  
Drug Targets ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Myelogenous Leukemia ◽  
Tki Resistance

AbstractIdentifying novel drug targets to overcome resistance to tyrosine kinase inhibitors (TKIs) and eradicating leukemia stem/progenitor cells are required for the treatment of chronic myelogenous leukemia (CML). Here, we show that ubiquitin-specific peptidase 47 (USP47) is a potential target to overcome TKI resistance. Functional analysis shows that USP47 knockdown represses proliferation of CML cells sensitive or resistant to imatinib in vitro and in vivo. The knockout of Usp47 significantly inhibits BCR-ABL and BCR-ABLT315I-induced CML in mice with the reduction of Lin−Sca1+c-Kit+ CML stem/progenitor cells. Mechanistic studies show that stabilizing Y-box binding protein 1 contributes to USP47-mediated DNA damage repair in CML cells. Inhibiting USP47 by P22077 exerts cytotoxicity to CML cells with or without TKI resistance in vitro and in vivo. Moreover, P22077 eliminates leukemia stem/progenitor cells in CML mice. Together, targeting USP47 is a promising strategy to overcome TKI resistance and eradicate leukemia stem/progenitor cells in CML.

Sign in / Sign up

Export Citation Format

Share Document