1. KIR Genes Associated With MDS Risk CCO Independent Conference Highlights of the 2015 ASCO Annual Meeting*
May 29 - June 2, 2015
*CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs.
This program is supported by educational grants from AstraZeneca, Bayer, Bristol-Myers Squibb, Celgene Corporation, Genentech, Incyte, and Novartis.

2. Myelodysplastic Syndrome
Spectrum of clonal hematopoetic disorders[1]
Relatively rare
In the US, only 4 new cases per 100,000 persons each yr
Syndrome marked by ineffective hematopoiesis and dysplastic cytologic features
Risk of development of secondary AML
MDS mortality risk correlates to score on revised IPSS[2]
AML, acute myeloid leukemia; IPSS, International Prognosis Scoring System; MDS, myelodysplastic syndrome.
1. Garcia-Manero G, et al. Am J Hematol. 2014;89: Greenberg PL, et al. Blood. 2012;120:

3. Natural Killer Cells
Cytotoxic blood lymphocytes important in tumor surveillance and infectious disease control[1]
5% to 15% of peripheral blood lymphocytes
Do not require previous antigen sensitization
Phenotype: CD3- CD56+
Large array of activating and inhibitory killer cell immunoglobulin-like receptors
Inhibitory receptors: 2 or 3 extracellular domains, long cytoplasmic tail[2]
Ligands: HLA class I
Activating KIR receptors: 2 or 3 extracellular domains, short cytoplasmic tail[2]
Ligands: tumor ligands MICA, MICB, ULBP
1. Terszowski G, et al. Swiss Med Wkly. 2012;142:w Kaur G, et al. Brain. 2013;136:

4. KIR Gene Complex Chromosome 19q13.4[1]
Haplotype A: only 1 activating KIR gene
Haplotype B: ≥ 1 of 6 activating KIR genes
Pts with higher number of activating KIR genes associated with significant risk reduction in developing childhood ALL[2]
Current study sought to determine if association exists between number of activating KIR genes and risk of MDS[3]
ALL, acute lymphocytic leukemia; KIR, killer cell immunoglobulin-like receptors; MDS, myelodysplastic syndrome.
1. Moussa P, et al. Front Immunol. 2013;18: Almalte Z, et al. Blood. 2011;8: Daher M, et al. ASCO Abstract 7001.

5. KIR Gene Study in MDS: Study Design and Pt Characteristics
Case control study
MDS pts (n = 180) compared with healthy controls (n = 117)
MDS pts both high risk (n = 60) and low risk (n = 120) by IPSS
MDS Pt Characteristics
Characteristic, %
Low-Risk MDS
(n = 120)
High-Risk MDS
(n = 60)
Male sex 72 70
Age older than 60 yrs 88 87
AML transformation 12 22
Previously treated 29 34
AML, acute myeloid leukemia; IPSS, International Prognostic Scoring System; KIR, killer cell immunoglobulin-like receptors; MDS, myelodysplastic syndrome.
Daher M, et al. ASCO Abstract Reprinted with permission.

6. KIR Gene Study in MDS: Analysis
Pt DNA samples from Leukemia Biobank at M.D. Anderson Cancer Center
Analysis of KIR genes by PCR
Samples correlated for phenotypic, genotypic, and outcome data
Logistic regression model used to study relationship of number of activating KIR genes and MDS risk category
KIR, killer cell immunoglobulin-like receptors; MDS, myelodysplastic syndrome.
Daher M, et al. ASCO Abstract 7001.

7. KIR Gene Study: Number of Activating KIR Genes Associated With Risk of MDS
Each additional activating KIR gene conferred protective effect against development of high-risk MDS
No independent survival benefit seen with higher number of activating KIR genes
No association shown between number of activating KIR genes and AML transformation
P =
P = .009
P = .04 60 50
Number of activating KIRs
0 or 1
2 or 3
4 or more 40
Frequencies (%) 30 20
AML, acute myeloid leukemia; IPSS, International Prognostic Scoring System; KIR, killer cell immunoglobulin-like receptors; MDS, myelodysplastic syndrome. 10
High IPSS
Low IPSS
Healthy Control
Daher M, et al. ASCO Abstract Reprinted with permission.

8. KIR Gene Study: Conclusions
Inheritance of a lower number of activating KIR genes associated with increased risk of developing MDS
Low number of activating KIR genes associated with a high- risk score (IPSS) in MDS pts
Each additional activating KIR gene in pts appears to lower risk of high-risk MDS
Future directions: development of immunotherapies for MDS using NK cells
IPSS, International Prognostic Scoring System; KIR, killer cell immunoglobulin-like receptors; MDS, myelodysplastic syndrome; NK, natural killer.
Daher M, et al. ASCO Abstract 7001.

9. Go Online for More CCO Coverage of ASCO 2015!
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