Smokers with chronic myeloid leukemia are at a higher risk of disease progression and premature death

Lauseker, Michael; Hasford, Joerg; Saußele, Susanne; Kremers, Stephan; Kraemer, Doris; Lindemann, Walter; Hehlmann, Rüdiger; Pfirrmann, Markus

doi:10.1002/cncr.30636

Cited by 19 publications

(14 citation statements)

References 26 publications

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“…The potential expression of these enzymes in CML cells may also be a factor in drug efficacy, or indeed drug resistance. Indeed, our findings provide a mechanistic rationale for the recent report that CML patients that are smokers are at increased risk of disease progression and premature death ( Lauseker et al, 2017 ).…”

Section: Discussionsupporting

confidence: 54%

Novel Pathways of Ponatinib Disposition Catalyzed By CYP1A1 Involving Generation of Potentially Toxic Metabolites

Lin

Kostov

Huang

et al. 2017

J Pharmacol Exp Ther

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Ponatinib, a pan-BCR-ABL tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia (CML), causes severe side effects including vascular occlusions, pancreatitis, and liver toxicity, although the underlying mechanisms remain unclear. Modifications of critical proteins through reactive metabolites are thought to be responsible for a number of adverse drug reactions. In vitro metabolite screening of ponatinib with human liver microsomes and glutathione revealed unambiguous signals of ponatinib-glutathione (P-GSH) adducts. Further profiling of human cytochrome P450 (P450) indicated that CYP1A1 was the predominant P450 enzyme driving this reaction. P-GSH conjugate formation paralleled the disappearance of hydroxylated ponatinib metabolites, suggesting the initial reaction was epoxide generation. Mouse glutathione S-transferase p1 (mGstp1) further enhanced P-GSH adduct formation in vitro. Ponatinib pharmacokinetics were determined in vivo in wild-type (WT) mice and mice humanized for CYP1A1/2 and treated with the CYP1A1 inducers 2,3,7,8-tetrachlorodibenzodioxin or 3-methylcholanthrene. Ponatinib exposure was significantly decreased in treated mice compared with controls (7.7- and 2.2-fold for WT and humanized CYP1A1/2, respectively). Interestingly, the P-GSH conjugate was only found in the feces of CYP1A1-induced mice, but not in control animals. Protein adducts were also identified by liquid chromatography–tandem mass spectrometry analysis of mGstp1 tryptic digests. These results indicate that not only could CYP1A1 be involved in ponatinib disposition, which has not been previously reported, but also that electrophilic intermediates resulting from CYP1A1 metabolism in normal tissues may contribute to ponatinib toxicity. These data are consistent with a recent report that CML patients who smoke are at greater risk of disease progression and premature death.

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Section: Discussionsupporting

confidence: 54%

Novel Pathways of Ponatinib Disposition Catalyzed By CYP1A1 Involving Generation of Potentially Toxic Metabolites

Lin

Kostov

Huang

et al. 2017

J Pharmacol Exp Ther

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“…These findings emphasized the urgent need to strengthen smoking control to reduce the CML burden. A previous study revealed that smoking might be an adverse prognostic factor, shortening survival time and contributing to CML's progression [ 42 ]. The smoking prevalence declined in most countries during the research, especially in high-income countries [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Trends in disease burden of chronic myeloid leukemia at the global, regional, and national levels: a population-based epidemiologic study

Ning

et al. 2020

Exp Hematol Oncol

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Background Outcomes of chronic myeloid leukemia (CML) has been improved dramatically in the past two decades, but survival levels of CML patients varied in regions. Comprehensive epidemiological research is necessary to evaluate the global burden of CML. Methods All data used in our study came from the Global Burden of Disease (GBD) study 2017. Incidence cases, death cases, disability-adjusted life-years (DALYs), and its corresponding age-standardized rate between 1990 to 2017 were used to describe the distribution of CML burden, according to age, sex, social-demographic index (SDI), and countries. Data about attributable risk factors contributing to CML deaths and DALYs were also extracted and analyzed. Results Globally, the disease burden of CML gradually decreased from 1990 to 2017. Higher SDI countries achieved a remarkable effect on diminishing the CML burden. Conversely, due to population growth, the incidence cases, death cases, and DALYs of CML in lower SDI quintiles showed an upward trend. India had the most incidence cases and death cases of CML in the world. Additionally, smoking was the most significant attributable risk factor contributing to CML deaths and DALYs, followed by high body mass index. Conclusion The disease burden of CML decreased globally, especially in higher SDI countries in the past 28 years. The increasing incidence cases and death cases were mainly observed in lower SDI countries. Additionally, strategies to control modifiable risk factors such as smoking and high body mass index might be useful in diminishing mortality and DALYs.

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“…Tobacco smoking is a risk factor for death and disease‐specific death in several cancers, including acute myeloid leukaemia 14–17 . Similarly, in a study investigating long‐term effects of imatinib treatment, in patients with chronic myeloid leukaemia (CML), smoking increased the risk of death and disease progression 18 . Smoking is a suspected risk factor for both acute and chronic myeloid leukaemia, similar to what has been proposed in MPNs 19,20 …”

Section: Introductionmentioning

confidence: 75%

Smoking impairs molecular response, and reduces overall survival in patients with chronic myeloproliferative neoplasms: A retrospective cohort study

et al. 2020

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Summary The effects of smoking on the molecular response (MR) and overall survival (OS) in patients with chronic myeloproliferative neoplasms (MPNs) have not been investigated before. We analysed a historical cohort of 498 consecutive patients diagnosed with MPNs. Moreover, we analysed a subgroup of 270 consecutive patients with MPNs with > 1 measurement of the JAK2V617F variant allele frequency. The data were analysed using Kaplan–Meier plots and Cox regression analysis, along with linear regression models. In all patients, the rate of MR was significantly higher in never‐smokers compared with current smokers in the univariate model (HR, 1·9; 95% CI, 1·1–3·3; P = 0·033) and the multivariate model (HR, 1·9; 95% CI, 1·1–3·5; P = 0·029). Similar findings were observed with different cut‐off values for a partial MR. A subgroup analysis including only interferon‐α2‐treated patients showed similar results. In multivariate analyses, the OS was significantly better for never‐smokers (HR, 0·46; 95% CI, 0·29–0·75; P = 0·002) than current smokers. The differences were more pronounced in the pegylated interferon‐α2‐treated patients. However, no significant interaction of interferon‐α2 treatment was observed. In conclusion, we found that tobacco smoking reduced the rate of MR and OS in patients with MPNs. Cessation of smoking should be encouraged.

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Smokers with chronic myeloid leukemia are at a higher risk of disease progression and premature death

Cited by 19 publications

References 26 publications

Novel Pathways of Ponatinib Disposition Catalyzed By CYP1A1 Involving Generation of Potentially Toxic Metabolites

Novel Pathways of Ponatinib Disposition Catalyzed By CYP1A1 Involving Generation of Potentially Toxic Metabolites

Trends in disease burden of chronic myeloid leukemia at the global, regional, and national levels: a population-based epidemiologic study

Smoking impairs molecular response, and reduces overall survival in patients with chronic myeloproliferative neoplasms: A retrospective cohort study

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