Dasatinib may overcome the negative prognostic impact of KIR2DS1 in newly diagnosed patients with chronic myeloid leukemia

Ali, Sara; Sergeant, Ruhena; O’Brien, Stephen G.; Foroni, Letizia; Hedgley, Corinne; Gerrard, Gareth; Milojković, Dragana; Stringaris, Kate; Khoder, Ahmad; Alsuliman, Abdullah; Gilleece, Maria; Gabriel, Ian; Cooper, Nichola; Goldman, John M.; Apperley, Jane F.; Clark, Richard E.; Marín, David; Rezvani, Katayoun

doi:10.1182/blood-2012-04-421016

Cited by 12 publications

(9 citation statements)

References 10 publications

(10 reference statements)

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“…KIR genotyping in 174 CML patients on first-line therapy with imatinib showed that the expression of KIR2DS1 was accompanied by a significantly lower 2-year probability to achieve cytogenetic response (Marin et al, 2012). In contrast, another study showed no significant impact of the KIR genotype on clinical outcome in 130 CML patients (Ali et al, 2012). However, missing KIR ligand KIR/HLA genotype combination might be a prognostic factor as in the case of increased survival in neuroblastoma patients treated with anti-GD2 antibody (Tarek et al, 2012).…”

Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 92%

Novel immune modulators used in hematology: impact on NK cells

Krieg

Ullrich

2013

Front. Immun.

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There is a wide range of important pharmaceuticals used in treatment of cancer. Besides their known effects on tumor cells, there is growing evidence for modulation of the immune system. Immunomodulatory drugs (IMiDs®) play an important role in the treatment of patients with multiple myeloma or myelodysplastic syndrome and have already demonstrated antitumor, anti-angiogenic, and immunostimulating effects, in particular on natural killer (NK) cells. Tyrosine kinase inhibitors are directly targeting different kinases and are known to regulate effector NK cells and expression of NKG2D ligands (NKG2DLs) on tumor cells. Demethylating agents, histone deacetylases, and proteasome inhibitors interfere with the epigenetic regulation and protein degradation of malignant cells. There are first hints that these drugs also sensitize tumor cells to chemotherapy, radiation, and NK cell-mediated cytotoxicity by enhanced expression of TRAIL and NKG2DLs. However, these pharmaceuticals may also impair NK cell function in a dose- and time-dependent manner. In summary, this review provides an update on the effects of different novel molecules on the immune system focusing NK cells.

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Section: Tyrosine Kinase Inhibitorsmentioning

confidence: 92%

Novel immune modulators used in hematology: impact on NK cells

Krieg

Ullrich

2013

Front. Immun.

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“…*KIR2DS4DEL refers to the 2DS4 allelic variant bearing a 22-bp deletion, also referred to as KIR1D. 24 In contrast, Kreutzman et al 25 showed an association between superior molecular response and KIR2DL5A/B NEG in a dasatinib-treated cohort. Observations of the British imatinib and Scandinavian cohorts, together with the current study, demonstrate the strongest link between KIR2DL5B of the KIR cluster and treatment outcomes.…”

Section: Pos and Kir2dl5bmentioning

confidence: 99%

KIR2DL5B genotype predicts outcomes in CML patients treated with response-directed sequential imatinib/nilotinib strategy

Yeung

Tang

Vidovic

et al. 2015

Blood

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“…Recently, some reports have suggested that the occurrence of CML, the disease course, and patient response to TKI therapy could be influenced by inhibitory and activating receptors regulating NK cell function within the immune system [13][14][15][16][17]. However, the preliminary findings of these studies are somewhat heterogenous.…”

mentioning

confidence: 99%