• The Journal of Internal Korean Medicine
• /
• v.37 no.2
• /
• pp.202-211
• /
• 2016

Objective: This clinical study reports on a case of generalized edema with hypoalbuminemia and pleural effusion improved by combined traditional Korean and Western medical treatments in a patient with chronic myeloid leukemia medicated with dasatinib.Method: Combined traditional Korean and Western medical treatment was carried out, including herbal medicine, acupuncture, moxibustion, and albumin injection. We examined the serum albumin, measured the circumference of both thighs and ankles to estimate the volume of the edema, and evaluated the pleural effusion symptoms.Results: The serum albumin increased, and generalized edema and pleural effusion improved significantly after the administration of Bojungchiseub-tang-gami.Conclusion: These results showed that complications of generalized edema and pleural effusion associated with dasatinib medication have the potential to be improved via combined traditional Korean and Western medical treatments.

• Biomolecules & Therapeutics
• /
• v.28 no.1
• /
• pp.1-17
• /
• 2020

Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exert suppressive function on the immune response. MDSCs expand in tumor-bearing hosts or in the tumor microenvironment and suppress T cell responses via various mechanisms, whereas a reduction in their activities has been observed in autoimmune diseases or infections. It has been reported that the symptoms of various diseases, including malignant tumors, can be alleviated by targeting MDSCs. Moreover, MDSCs can contribute to patient resistance to therapy using immune checkpoint inhibitors. In line with these therapeutic approaches, diverse oligonucleotide-based molecules and small molecules have been evaluated for their therapeutic efficacy in several disease models via the modulation of MDSC activity. In the current review, MDSC-targeting oligonucleotides and small molecules are briefly summarized, and we highlight the immunomodulatory effects on MDSCs in a variety of disease models and the application of MDSC-targeting molecules for immuno-oncologic therapy.

• BLOOD RESEARCH
• /
• v.53 no.4
• /
• pp.294-298
• /
• 2018

Background Production of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert $CD4^+CD25^-$ conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters. Methods Thirty-seven newly diagnosed CN-AML patients were enrolled in our study along with 22 healthy individuals. The expression of the IDO and FOXP3 genes was analyzed by SYBR Green real-time PCR. Results Both IDO and FOXP3 were highly upregulated in CN-AML patients compared to control groups (P=0.004 and P=0.031, respectively). A positive correlation was observed between IDO and FOXP3 expression among AML patients (r=0.512, P=0.001). Expression of IDO and FOXP3 showed no significant correlation with laboratory parameters such as white blood cell and platelet counts, hemoglobin levels, bone marrow blast percentage, gender, and FLT3 mutation status (P>0.05). Conclusion Higher IDO expression in CN-AML patients may be associated with an increased Treg phenotype which may promote disease progression and lead to poor prognosis of CN-AML patients.

• Oncology Letters
• /
• v.41 no.5
• /
• pp.2625-2635
• /
• 2019

The majority of natural killer (NK) cells serve an important role in eliminating malignant cells. The cytotoxic effects of NK cells were first identified against leukemia cells, and it is now hypothesized that they may have a critical role in leukemia therapy. The cellular functions of NK cells are mediated by their cell surface receptors, which recognize ligands on cancer cells. The role of NK cells is specifically regulated by the activating or inhibitory killer cell immunoglobulin-like receptors (KIRs) on their surface, which bind to the human leukocyte antigen (HLA) class I ligands present on the target cells. The association between KIR and HLA is derived from the diversity of KIR/HLA gene profiles present in different individuals, and this determines the cytotoxic effect of NK cells on cancer cells. Chronic myeloid leukemia (CML) is a hematological leukemia characterized by the hyper-proliferation of myeloid cells, with the majority of patients with CML presenting with abnormal immune cells. Tyrosine kinase inhibitors are the present standard therapy for CML, but are associated with numerous adverse side effects. Various studies have proposed CML therapy by immunotherapeutic approaches targeting the immune cells. This review summarizes the contents of NK cells and the association between KIR/HLA and leukemia, especially CML. This is followed by a discussion on the development of NK cell immunotherapy in hematological malignancies and research into strategies to enhance NK cell function for CML treatment.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• v.31 no.6
• /
• pp.535-540
• /
• 2009

Proliferation of abnormal hematopoietic cells with impaired differentiation, regulation and programmed cell death leads to leukemia. AML(acute myeloid leukemia) is a malignancy with malfunction of myeloid hematopoietic cells with acute behavior. The oral manifestations of the disease are posterior palate hemorrhage, gingival bleeding and gingival ulceration as a result of infection by normal oral flora and gingival infiltration by leukemic cells. A 49-year-old male patient was referred from local dental clinic. The patient was diagnosed with AML FAB M1 (acute myeloid leukemia French-American-British classification M1 myeloblastic leukemia without maturation). The oral infection focus was removed by a conservative treatment. 2 days after the dental treatment, the patient underwent chemotherapy. At 8-month follow-up, the overall outcome was excellent. Oral manifestations of AML are often the first indications of the malignancy. Therefore it is essential for dentists, especially oral and maxillofacial surgeons, to be aware of the diagnostic signs and complications associated with leukemia for better diagnosis and subsequent treatment and management.

• Korean Journal of Clinical Pharmacy
• /
• v.26 no.1
• /
• pp.53-58
• /
• 2016

Objective: To estimate the association between ABCG2 C421A polymorphism and response to imatinib in chronic myeloid leukemia. Methods: A systematic review was conducted to evaluate the effect of ABCG2 C421A polymorphism on imatinib response. The databases of PubMed, Embase, Web of science, CINAHL with FullText, and Cochrane Library were searched for all published studies from inception to December 2015. The following terms were used with functions of 'AND' and 'OR': 'chronic myeloid leukemia', 'CML', 'drug transporter', 'ABCG2', 'BCRP', 'polymorphisms', 'SNPs', and 'imatinib'. The studies reporting the association between ABCG2 polymorphism and imatinib response were evaluated. Results: A total of 7 studies were included in the present meta-analysis. The pooled analysis showed that ABCG2 c.421CC genotype was significantly associated with poor response to imatinib under the dominant model (CC vs CA+AA; OR: 0.56; 95% CI: 0.41, 0.77; p = 0.0004). The subgroup analysis of Asian studies demonstrated a significantly lower response in c.421CC genotype than in c.421CA or c.421AA genotype (OR: 0.52; 95% CI: 0.37, 0.73; p = 0.0002). In subgroup analyses of 5 studies, the patients with the c.421CC genotype exhibited higher risk for worse response than the patients with c.421CA or c.421AA genotype (heterozygote codominant model: CC vs. AC; OR: 0.49, 95% CI: 0.33, 0.73; p = 0.0006; homozygote codominant model: CC vs AA; OR: 0.43; 95% CI: 0.25, 0.75, p = 0.003). Conclusion: The ABCG2 c.421CC genotype was significantly associated with poor response to imatinib compared to the c.421CA and c.421AA genotypes in chronic myeloid leukemia, especially in Asian patients.

• Investigative Magnetic Resonance Imaging
• /
• v.13 no.1
• /
• pp.88-92
• /
• 2009

Granulocytic sarcoma is a rare extramedullary tumor composed of immature granulocytic precursors. Usually, granulocytic sarcoma is seen in association with acute myeloid leukemia, or other myeloproliferative disorders. Rarely, it may manifest as a primary presentation before the onset of systemic disease in acute myeloid leukemia. The clinical suspicion of granulocytic sarcoma based on imaging findings is important for the management of the patient especially when systemic disease of acute myeloid leukemia is not confirmed as in our case. We report the MR findings of a granulocytic sarcoma in the left leg mimicking hemorrhagic abscess in a patient with acute myeloid leukemia. We believe that MRI can be a helpful diagnostic method of making a differential diagnosis of granulocytic sarcoma in a patient with leukemia, and this can be done by analyzing the signal intensity and the enhancement pattern.

• Genomics & Informatics
• /
• v.13 no.2
• /
• pp.45-52
• /
• 2015

Acute myeloid leukemia is a well characterized blood cancer in which the unnatural growth of immature white blood cell takes place, where several genes transcription is regulated by the micro RNAs (miRNAs). Argonaute (AGO) protein is a protein family that binds to the miRNAs and mRNA complex where a strong binding affinity is crucial for its RNA silencing function. By understanding pattern recognition between the miRNAs-mRNA complex and its binding affinity with AGO protein, one can decipher the regulation of a particular gene and develop suitable siRNA for the same in disease condition. In the current work, HOXA9 gene has been selected from literature, whose deregulation is well-established in acute myeloid leukemia. Four miRNAs (mir-145, mir-126, let-7a, and mir-196b) have been selected to target mRNA of HOXA9 (NCBI accession No. NM_152739.3). The binding interaction between mRNAs and mRNA of HOXA9 gene was studied computationally. From result, it was observed mir-145 has highest affinity for HOXA9 gene. Furthermore, the interaction between miRNAs-mRNA duplex of all chosen miRNAs are docked with AGO protein (PDB ID: 3F73, chain A) to study their interaction at molecular level through an in silico approach. The residual interaction and hydrogen bonding are inspected in Discovery Studio 3.5 suites. The current investigation throws light on understanding of AGO-assisted miRNA based gene silencing mechanism in HOXA9 gene associated in acute myeloid leukemia computationally.

• Asian Pacific Journal of Cancer Prevention
• /
• v.13 no.9
• /
• pp.4215-4220
• /
• 2012

AML (Acute myeloid leukemia) is a form of blood cancer where growth of myeloid cells occurs in the bone marrow. The prognosis is poor in general for many reasons. One is the presence of leukaemia-specific recognition markers such as FLT3 (fms-like tyrosine kinase 3). Another name of FLT3 is stem cell tyrosine kinase-1 (STK1), which is known to take part in proliferation, differentiation and apoptosis of hematopoietic cells, usually being present on haemopoietic progenitor cells in the bone marrow. FLT3 act as an independent prognostic factor for AML. Although a vast literature is available about the association of FLT3 with AML there still is a need of a brief up to date overview which draw a clear picture about this association and their effect on overall survival.

• Korean Journal of Clinical Pharmacy
• /
• v.19 no.2
• /
• pp.89-95
• /
• 2009

Gemtuzumab ozogamicin (GO) is an antibody-targeted chemotherapeutic agent consisting of calicheamicin, a potent cytotoxic antibiotic linked to a recombinant humanized anti CD33 monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). GO is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. GO has shown moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myeloid leukaemia, with more promising results in acute promyelocytic leukaemia. The side effect profile may be an improvement on conventional chemotherapy, except for a higher frequency of veno-occlusive disease or sinusoidal obstructive syndrome, especially after a subsequent haematopoietic stem cell transplantation. Because of the different mechanisms of action and non-overlapping toxicities, the integration of this immunoconjugate with standard chemotherapy is a rational approach.