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KRAS is a frequently mutated gene in colorectal cancer. In addition, PIK3CA mutations commonly co-exist with KRAS mutations and lead to additive activation of the PI3K/mTOR signaling pathway. Here, we investigated preclinical activity of gedatolisib, a PI3K/mTOR dual inhibitor, to identify mechanism of inhibition of PI3K/mTOR in 28 colorectal cancer (CRC) cells. Cells specifically with PIK3CA mutation were sensitive while those with KRAS mutation were resistant to gedatolisib. 9 out of 28 CRC cells harbor PIK3CA & KRAS co-mutation and 7 out them were shown to be sensitive to gedatolisib. However, HCT15 and LS174T cells were resistant. We identified that resistant cell lines have high activity of GSK3B and TCF7 frameshift mutation (465insertC466;H155fs*), which functions as positive regulator of WNT/b-catenin pathway. The effects of GSK3B-knockdown showed decreased activity of mTOR downstream molecules in gedatolisib-treated resistant cells. Interestingly, these effects also caused a decrease in activity of WNT/b-catenin pathway. In addition, combination treatment of gedatolisib and CHIR-99021, GSK3B inhibitor, resulted in significantly enhanced cytotoxicity against gedatolisib-resistant TCF7 frameshift mutant cells. Taken together, these show that aberrant regulation of WNT/b-catenin pathway and high activity of GSK3B by TCF7 frameshift mutation cause resistance to PI3K/mTOR dual inhibitor. Inhibition of GSK3B activity in colorectal cancer cells with KRAS and PIK3CA co-mutations increases sensitivity to PI3K/mTOR dual inhibitor. Citation Format: Ye-Lim Park, Hwang-Phill Kim, Seul-Ki Cheon, Jun-Kyu Kang, Yoojoo Lim, Sang-Hyun Song, Sae-Won Han, Tae-you Kim. Activation of WNT/b-catenin signaling results in resistance to PI3K/mTOR dual inhibitor in co-existing KRAS and PIK3CA mutant colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5214. doi:10.1158/1538-7445.AM2017-5214

Although MEK blockade has been highlighted as a promising anti-tumor drug, it has poor clinical efficacy in KRAS mutant colorectal cancer. Several feedback systems have been described in which inhibition of one intracellular pathway leads to activation of a parallel signaling pathway, thereby decreasing the effectiveness of single-MEK targeted therapies. In this study, we describe a feedback mechanism in which MEK inhibition leads to activation of macrophage migration inhibitory factor (MIF)-induced stat3 signaling pathway in KRAS mutant colorectal cancer (CRC) cells. We found that KRAS mutant CRC cells with refametinib, MEK inhibitor, induced MIF secretion and resulted in activation of Stat3. MIF knockdown by siRNA partially restored sensitivity to refametinib in KRAS mutant cells. In addition, combination with refametinib and 4IPP, a MIF inhibitor, effectively reduced the activity of stat3 and MAPK, more than single agent treatment. As a result, combined therapy was found to exhibit a synergistic growth inhibitory effect against refametinib-resistant cells by downregulating MIF expression. These results reveal that MIF-induced stat3 activation evoked an intrinsic resistance to refametinib. Our results provide the basis for a rational combination strategy against KRAS mutant colorectal cancers, predicated on the understanding of cross-talk between the MEK and MIF pathways. Citation Format: Seul-Ki Cheon, Hwang-Phill Kim, Ye-Lim Park, Si Hyun Lee, Jun-Kyu Kang, Yoojoo Lim, Sang-Hyun Song, Sae-Won Han, Tae-You Kim. MIF-induced stat3 activation promotes resistance to MEK blockade in KRAS mutant colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3167. doi:10.1158/1538-7445.AM2017-3167

10008 Background: Cancer-related fatigue(CRF) is a common and severe symptom in patients with cancer. The purpose of this study is to evaluate the anti-fatigue effect of Korean Red Ginseng(Steamed Panax ginseng C.A. Meyer) on patients with colorectal cancer. Methods: 438 colorectal cancer patients in treatment with mFOLFOX-6 regimen were randomly assigned to either the Korean Red Ginseng[KRG](n = 219) or placebo(n = 219) group and received 2,000 mg/day test substances for 16 weeks. The primary endpoint was the Area Under Curve(AUC) of Brief Fatigue Inventory(BFI) over 16 weeks. The AUC and change from the baseline were calculated. The frequency and types of adverse events were determined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Results: 438 colorectal cancer patients were enrolled from 15 institutions. Changes from the baseline in the global BFI were 78.54(Standard deviation [SD] = 16.91) in KRG group vs. 75.89(SD = 16.85) in placebo group at 16 weeks(P = 0.0363). Changes from the baseline in the Usual Fatigue were 76.15 (SD = 17.08) in KRG group vs. 73.08(SD = 17.03) in placebo group at 16 weeks(P = 0.0454). Changes from the baseline in the Mood were 80.46(SD = 17.16) in KRG group vs. 77.88(SD = 17.59) in placebo group at 16 weeks(P = 0.0086). Changes from the baseline in the Relations with Others were 82.09(SD = 17.49) in KRG group vs. 78.67(SD = 17.90) in placebo group at 16 weeks(P = 0.0080). Changes from the baseline in the Walking ability were 82.70(SD = 17.28) in KRG group vs. 80.77(SD = 16.47) in placebo group at 16 weeks(P = 0.0090). Changes from the baseline in the Enjoyment of life were 79.53(SD = 19.53) in KRG group vs. 77.51(SD = 18.02) in placebo group at 16 weeks(P = 0.0150). Toxicities per self-report and CTCAE grading did not differ statistically significantly between the groups. Conclusions: The data supports benefits of consuming 2,000 mg KRG water extract powder daily on CRF over 16-week period. There were no discernible toxicities associated with the treatment. More studies on mechanisms of KRG to guide its role in CRF improvement are needed. Clinical trial information: NCT02039635.

Although induction chemotherapy can reduce distant metastases in locally advanced head and neck squamous cell carcinoma (HNSCC), overall survival (OS) improvement because of induction chemotherapy has not been confirmed.We reviewed medical records of 224 patients diagnosed with locally advanced HNSCC who were treated with induction chemotherapy followed by concurrent chemoradiotherapy (CRT; induction chemotherapy/CRT; N = 144) and CRT alone (N = 80) from 2005 to 2013. We analyzed OS and progression-free survival (PFS).The 3-year OS rate was significantly higher in the induction chemotherapy/CRT group compared to the CRT group (74.0% vs 62.7%; p = .045). The 3-year PFS rate was 64.6% in the induction chemotherapy/CRT group and 54.1% in the CRT group (p = .060). Subgroup analysis showed patients with high N classification (N2 or N3) oropharyngeal cancer had greater benefits when treated with induction chemotherapy/CRT.Induction chemotherapy plus CRT improved OS, compared to CRT alone in locally advanced HNSCC, especially with high N classification.

Introduction: Regorafenib is an oral multikinase inhibitor with anti-angiogenic activity. Decrease in tumor density without significant decrease in tumor volume is often observed after treatment with the drug, suggesting the necessity of further means of response evaluation in addition to size criteria. This study was planned to evaluate whether metabolic imaging with 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) could predict outcome in mCRC patient treated with regorafenib. Methods: Patients were enrolled into a main study entitled Identification of Predictive Biomarker of Regorafenib in Refractory Colorectal Cancer: A Prospective Explorative Study (NCT01996969). mCRC patients (N = 117) were treated with regorafenib, 160mg orally once daily, on days 1-21 of a 28-day cycle, and treatment outcome was evaluated according to the Response Evaluation Criteria in Solid Tumors 1.1. For this imaging sub-study, the results of 18-FDG PET scans obtained at baseline and after 2 cycles of treatment were analyzed. Total lesion glycolysis (TLG) of each patient was calculated by multiplying the volume exceeding the threshold of 40% of maximum standardized uptake value (SUV) by the mean SUV of the lesion, and the percentage changes of TLG after treatment were calculated. The association between the changes of the metabolic imaging and treatment outcome was analyzed. Results: A total of 44 patients were evaluable for 18-FDG PET scan results. The best overall response in the 44 patients were, partial response in 3 (6.8%), stable disease in 23 (52.3%) and progressive disease in 18 (40.9%). The median progression-free survival (PFS) and the median overall survival (OS) were 5.4 and 14.1 months, respectively. The median of TLG at baseline was 187.4 (range 18.3 to 8893.2). After 2 cycles of regorafenib, 50.0% of patients had a decrease in TLG. Median change in TLG was 1.7% (range, -75.7 to 251.6%). Changes in TLG were modestly associated with size changes (Pearson's r = 0.51, p = 0.001). Patients with lower baseline TLG (< 324.49) showed significantly longer OS (1 year survival rate 75.6 vs. 33.5%, p = 0.008). Moreover, patients showing higher decrease in TLG (change < 1.7%) showed significantly longer PFS (median 8.4 vs. 1.9 months, p Conclusions: Lower baseline TLG is associated with better OS and higher decrease in TLG after treatment predicted better PFS in mCRC patients treated with regorafenib. Citation Format: Yoojoo Lim, Ji-In Bang, Sae-Won Han, Jin Chul Paeng, Jeong Hee Yoon, Jeong Min Lee, Jae-Kyung Won, Gyeong Hoon Kang, Seung-Yong Jeong, Kyu Joo Park, Kyung-Hun Lee, Jee Hyun Kim, Tae-You Kim. Total lesion glycolysis (TLG) as an imaging biomarker of regorafenib treatment in metastatic colorectal cancer (mCRC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3972.

10067Background: Patients’ proper understanding and consent to participate are crucial for successful conduction of clinical trials (CT). We have conducted a survey, to assess the current patients’...

The nationwide statistical analysis of each disease of classical myeloproliferative neoplasm (MPN) in Korea has not been reported yet. To this end, we have analyzed incidence rates, survival rates and treatment pattern of polycythemia vera (PV), primary myelofibrosis (MF) and essential thrombocythemia (ET) using Korea National Cancer Incidence Database (KNCIDB) and Health Insurance Review and Assessment Service (HIRA) database. Between 2003 and 2011, a total of 4,342 new cases of MPN were reported to the KNCIDB. ET was the most common, followed by MF and PV. The crude incidence rates for PV, MF, and ET have increased during the period, reaching 0.40, 0.15, and 0.84 per 100,000, respectively. Five-year relative survival rate of all MPN patients was 89.3%, with lowest relative survival rate with MF (53.1%). The prevalence of each disease estimated from HIRA data also increased during the study period. Notably, ET was found to be most prevalent. The prescription rate of hydroxyurea and phlebotomy to PV, MF and ET patients remained constant over the period, and the prescription rate of hydroxyurea was higher in patients with age over 60 years. This is the first Korean nationwide statistics of MPN, using central registry data. This set of data can be utilized to compare the Korean MPN status to international data and guidelines., Graphical Abstract

In order to identify novel fusion transcripts in colorectal cancer, we carried out paired-end RNA sequencing in 28 human colorectal cancer cell lines. Fusion transcript candidates were identified using ChimeraScan and FusionMap tools. We obtained 1380 candidates having 4 or more read counts and spanning reads. Among the candidates, we selected 27 candidates for validation which harbors genes related to the Wnt signaling pathway or kinases according to KEGG or DAVID. After the targeted gene filtering step, validation using RT-PCR with fusion specific primers finally resulted in 2 intra- and 1 inter-fusion transcripts. Intra-fusion transcripts were NFATC3-PLA2G15 and AKAP13-PDE8A and inter-fusion transcript was KRT8-PKM2 each identified in colo-320, SW-480 and SNU-1235, respectively. The fusion junctions were confirmed by Sanger sequencing. NFATC3-PLA2G15 fusion transcripts consisted of exon 1-9 of NFATC3 (nuclear factor of activated T-cells, cytoplasmic 3) gene and exon 2-6 of the PLA2G15 (Phospholipase A2, Group 5) gene and both located on the same chromosome 16q. NFATC3 is known as transcription factor in the Wnt signaling pathway and regulates function of the target genes like cell proliferation, invasion and epithelial-to-mesenchymal transition (EMT). Under the experiments using siRNA in the colo-320 cell carrying fusion transcript, knockdown of the NFATC3-PLA2G15 fusion transcript decreased mRNA and protein expression of mesenchymal markers, namely vimentin (VIM), Twist-related protein 1 (TWIST1) and fibronectin (FN), and increased epithelial markers, E-cadherin (CDH1) and claudin-1 (CLDN1). Fusion transcripts knockdown also led to decrease of the invasion ability regulated by above markers. Moreover, soft agar assay showed inhibition of colony formation after fusion transcript knockdown. Fusion transcript downregulation also resulted in decrease of cell proliferation and mRNA and protein expression of cyclin D but increase in p27 level. The knockdown did not have influence in the fusion negative cell line. Collectively, these results suggest that the NFATC3-PLA2G15 fusion transcript is involved in invasion and proliferation of colorectal cancer cells. Citation Format: JE Jang, HP Kim, SH Lee, DW Lee, YJ Lim, SW Han, TY Kim. NFATC3-PLA2G15 fusion transcript identified by RNA-sequencing promotes tumor progression in colorectal cancer cells. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A28.

Introduction: Regorafenib is an oral multikinase inhibitor, which has anti-angiogenic and anti-tumor activity by inhibition of a number of angiogenic and oncogenic kinases. It induces distinct radiological changes in metastatic colorectal cancer (mCRC), which are decrease in tumor attenuation and cavitation of lung metastasis. These changes may be a result of anti-angiogenic activity, but the clinical implications of the changes are unclear. This study was designed to analyze the radiological changes in association with treatment outcome in mCRC patients treated with regorafenib. Methods: All patients were a part of a main study entitled Identification of Predictive Biomarker of Regorafenib in Refractory Colorectal Cancer: A Prospective Explorative Study (NCT01996969). Tumor attenuation measured by Hounsfield units (HU) of contrast-enhanced computed tomography (CT) scan and cavitary changes of lung metastases were evaluated in mCRC patients (N = 80) treated with regorafenib (160mg orally once daily, on days 1-21 of a 28-day cycle). Maximum standardized uptake values (mSUV) of tumor lesions at baseline and after 2 cycles of treatment were analyzed in patients whose 18-fluoro-deoxyglucose positron emission tomography (PET)-CT images were available for analysis. Treatment outcome was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The association between radiological changes and treatment outcome was analyzed. Results: A total of 141 lesions in 72 patients were analyzed with HU measurement. After 2 cycles of regorafenib treatment, 87.5% of patients had a decrease in tumor attenuation. Median change in tumor attenuation was -23.9% (range -61.5% to 20.7%). Lesional attenuation changes were modestly associated with changes in mSUV in PET-CT scans (Pearson's r = 0.38, p Conclusions: Regorafenib showed prominent anti-angiogenic activity in mCRC represented by the radiological changes. Although the changes were not associated with treatment outcome, it was persistently observed at the time of PD by RECIST 1.1. The results suggest the possibility of inadequacy of current conventional response evaluation paradigm in treating mCRC patients with regorafenib. We may need to develop alternative evaluation and treatment strategies considering the anti-angiogenic activity. Citation Format: Yoojoo Lim, Sae-Won Han, Jeong Hee Yoon, Jeong Min Lee, Jung Min Lee, Jin Chul Paeng, Jae-Kyung Won, Gyeong Hoon Kang, Seung-Yong Jeong, Kyu Joo Park, Kyung-Hun Lee, Jee Hyun Kim, Tae-You Kim. Clinical implications of anti-angiogenic effect of regorafenib in metastatic colorectal cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2015 Nov 5-9; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl 2):Abstract nr A2.

Sarcomatoid carcinoma of the lung is defined as a group of poorly differentiated non-small cell carcinomas that contain a component of sarcoma or a sarcoma-like element. Most sarcomatoid carcinomas are known to have a poor prognosis. We describe a 45-year-old female never smoker and 49-year-old female never smoker with sarcomatoid carcinomas of the lung that expressed a specific EGFR mutation: microdeletion of exon 19. Their cancers progressed rapidly, despite appropriate conventional chemotherapy. After they took the EGFR-targeted agent gefitinib, there was a dramatic reduction in tumor size. Sarcomatoid carcinoma of the lung is a rare cancer whose pathogenesis is not well understood. According to these cases, the EGFR mutation could be a driver mutation and the potential therapeutic target of EGFR-targeted agents for sarcomatoid carcinoma in lung cancer patients, especially never smokers. (Korean J Med 2013;84:446-451)

Purpose Exemestane has shown good efficacy and tolerability in postmenopausal women with hormone receptor-positive metastatic breast cancer. However, clinical outcomes in Korean patients have not yet been reported. Methods Data on 112 postmenopausal women with metastatic breast cancer were obtained retrospectively. Clinicopathological characteristics and treatment history were extracted from medical records. All patients received 25 mg exemestane daily until objective disease progression. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR=complete response+partial response+stable disease for 6 months). Results The median age of the subjects was 55 years (range, 28-76 years). Exemestane treatment resulted in a median PFS of 5.7 months (95% confidence interval [CI], 4.4-7.0 months) and median OS of 21.9 months (95% CI, 13.6-30.3 months). ORR was 6.4% and CBR was 46.4% for the 110 patients with evaluable lesions. Symptomatic visceral disease was independently associated with shorter PFS (hazard ratio, 3.611; 95% CI, 1.904-6.848; p

TO THE EDITOR: Heparin-induced thrombocytopenia (HIT) is a significant complication of heparin therapy. Risk factors for HIT include the type of heparin used, duration of heparin exposure, and clinical setting. Here, we report a 76-year-old man who presented with life-threatening pulmonary thromboembolism and deep-vein thrombosis, preceded by a dramatic decrease in platelet count 1 week after radical cystectomy for transitional cell bladder carcinoma. He was diagnosed with type II HIT caused by a small amount of unfractionated heparin mixed into his total parenteral nutrition (TPN) solution. One thousand units heparin per day were added to his TPN for 1 week. A heparin-platelet factor-4 antibody enzyme-linked immunosorbent assay of his serum was strongly positive. After cessation of TPN infusion, argatroban was started for thrombosis. His platelet count gradually increased to a normal level, and the thrombosis was treated successfully. This case suggests HIT should be suspected in patients with typical clinical manifestations and risk factors, even if the infused heparin dose is small. Heparin is widely used in a variety of medical therapies from the treatment of life-threatening acute thromboembolisms to the maintenance of indwelling vascular catheter patency. However, heparin therapy is often complicated by thrombocytopenia. The incidence of heparin-induced thrombocytopenia (HIT) in patients who receive heparin including unfractionated heparin and low-molecular-weight heparin is 0.1-5% [1]. There are 2 types of HIT. Type I HIT is a relatively common non-immune reaction that causes an asymptomatic, transient, and mild decrease in platelet count. In contrast, type II HIT is an immune complex disorder involving heparin bound to the platelet-specific chemokine, platelet factor-4 (PF4). These heparin-PF4 complexes activate both platelets and endothelial cells, resulting in platelet consumption and endothelial injury with thrombosis and disseminated intravascular coagulation [2]. Heparin use could go unnoticed if it is not applied as a conventional anticoagulant but rather as a supportive agent to maintain vasc,ular patency. However, unrecognized HIT can lead to life-threatening complications. Therefore, it is important to suspect HIT in patients who develop acute thrombosis or thrombotic tendency preceded by a decrease in platelet count during or soon after heparin therapy, even if the infused amount is small. Immediate discontinuation of heparin administration and initiating alternative anticoagulant therapy are critical for avoiding further thrombosis, even before laboratory results are available [3]. To the best of our knowledge, this is the first report on a patient who experienced type II HIT after low-dose heparin added to his total parenteral nutrition (TPN) for 1 week.

5552 Background: Although induction chemotherapy (IC) for LA-HNSCC has shown high response rates, some patients do not respond to IC. Surgery has been the usual choice for the non-responding patients, but practically, not all of these patients are eligible for operation. The purpose of this study was to evaluate the efficacy of definitive radiation therapy (RT) for the HNSCC patients who failed IC. Methods: We have retrospectively analyzed the outcome of patients with LA-HNSCC who were initially treated with IC at Seoul National University Hospital between Jan. 2006 and Dec. 2010. Chemotherapeutic regimens used were 5-FU/cisplatin, docetaxel/5-FU/cisplatin, and docetaxel/cisplatin with or without cetuximab. After IC, patients were treated with RT, concurrent chemoradiation (CCRT), or surgery, either alone or with postoperative RT. Treatment modality was chosen on multi-disciplinary basis of our institution. Response was evaluated using RECIST criteria. Results: A total of 225 LA-HNSCC patients treated with IC were analyzed. Median age was 54 (range 24-77). Primary tumor locations were oral cavity (39.5%), nasal cavity/paranasal sinus (13.1%), oropharynx (13.1%), nasopharynx (13.1%), larynx (7.9%) and hypopharynx (13.1%). Among the 225 patients, 38 (16.9%) patients did not respond to IC [stable diseases (SD) = 23 (10.2%), progressive disease (PD) = 15 (6.7%)], and their median overall survival was 14.5 months. Among the 38 non-responders, 14 (36.8%) patients were undertaken surgery and 22 (57.8%) unresectable or inoperable patients were treated with either definitive RT or CCRT. Responses to subsequent definitive RT or CCRT for 20 evaluable patients were as follows: complete response = 6 (30.0%), partial response = 7 (35.0%), SD = 3 (15.0%), PD = 4 (20.0%) Overall response rate to definitive RT or CCRT in non-responder to IC was 65.0% (95%CI: 44.1%- 85.9%). Nine out of 15 patients who showed PD to IC received definitive RT or CCRT and interestingly, 3 (33.3%) patients responded to definitive RT or CCRT. Conclusions: A significant portion of HNSCC patients who failed to IC can benefit from subsequent definitive RT or CCRT. Further prospective study is warranted.

Arsenic trioxide (As2O3) has shown substantial efficacy in the treatment of patients with acute promyelocytic leukemia (APL). However, since not all patients could achieve complete remission after As2O3 treatment, it is necessary to investigate a novel treatment method overcoming the resistance of current treatment. However, the therapeutic role of calcitriol against APL has not yet been fully elucidated. In our study, we investigated the anti-leukemic effect of calcitriol in combination with As2O3 on the human APL cell line HL-60. Inhibition of proliferation rate of HL-60 cells was measured by the trypan blue exclusion test was resulted in dose, time- dependent expressions. To evaluate the effects of combination treatment of As2O3 and calcitriol on the cell proliferation, we analyzed the combined effects of As2O3 and calcitriol using CalcuSyn software (BioSoft, Ferguson, MO, USA), which is based on the multiple drug-effect equation of Chou and Talalay (Chou TC, et al. Adv Enzyme Regul 1984): a combination index (CI) of 1 is defined as synergistic, additive, or antagonistic, respectively. In all combinations, the CI values calculated were less than 1. To investigate the effects of these treatments on the apoptosis pathway, we analyzed the expression of Bax, Caspase-3, Bcl-2 with the Western blot and the RT-PCR. In the Western blot analysis, lower Bcl-2 and higher Bax and Caspase-3 expressions were observed in the As2O3 or calcitriol-treated groups compared to the control group. The combination treatment decreased Bcl-2 expression and increased Bax and Caspase-3 expressions more prominently than the single treatment using either As2O3 or calcitriol. In the RT-PCR analysis, these trends were validated again with the same results. These cells were then labeled with fluorescein-conjugated Annexin V-FITC and propidium iodide (PI), and analyzed with flow cytometry to differentiate whether the main cause of cell death was apoptosis or necrosis. To resultsze, calcitriol in combination with As2O3 synergistically inhibited proliferation of the human APL cell line HL-60. In addition, calcitriol combined with As2O3 more prominently activated the apoptosis pathway than single treatment using either calcitriol or As2O3. The main cause of cell death was also apoptosis. Our results suggest that these novel findings could be applied to improve the therapeutic outcomes of patients with APL. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4909. doi:1538-7445.AM2012-4909

Abstract 5279 Background: There is a lack of clinical research regarding the effect of iron deficiency anemia on white blood cells (WBC).This study presents the incidence of leukopenia in patients with iron deficiency anemia and the relationship between the white blood cell count and the level of hemoglobin(Hb). Patients and Method: Medical records of patients over 12 years of age with iron deficiency anemia were reviewed. Patients with concomitant disease that may alter the WBC count such as hematologic malignancy, solid tumor, history of gastrectomy, vitamin B12 or folate deficiencies and active inflammation were excluded. Results: From January 2006 to December 2010, a total of 516 eligible patients were included. Median age was 47 years with female predominance (80.6%). Leukopenia was found in 91 patients (17.6%). The incidence of leukopenia was significantly higher in patients with hemoglobin level of less than 8 g/dL than those with higher level of hemoglobin (44/183, 24.0% vs. 47/333, 14.1%, P=0.005, Table 1). The levels of WBC count were found to decrease in accordance with the decrease in hemoglobin level (Pearson's coefficient: 0.178, P Conclusion: This study shows the high incidence of leukopenia in patients with iron deficiency anemia. The severity of leukopenia correlates with the decrease of hemoglobin in dose-dependent manner. Among the WBC subsets, lymphocyte count was significantly affected. Disclosures: No relevant conflicts of interest to declare.