t(8;21)(q22;q22) acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a high relapse rate in China. Two leukemic myeloblast populations (CD34
Gene Expression ; Granulocyte Precursor Cells ; Humans ; Immunophenotyping ; Leukemia, Myeloid, Acute/genetics* ; Membrane Glycoproteins ; Prognosis ; Proteins ; Proto-Oncogene Proteins c-kit/genetics*

OBJECTIVE: To analyze the characteristics of volatile organic compounds (VOCs) in expiratory air components of patients with acute promyelocytic leukemia (APL), and assess the feasibility of VOCs for the diagnosis and prognostic evaluation of APL. METHODS: The VOCs exhaled from the patients with APL and healthy volunteers should be analyzed with SPME-GC/MS, and compared between newly-diagnosed group, relapse group, remission group, and healthy group with Wilcoxon/Kruskal-Wallis one-way analysis of variance and Dunn-Bonferroni test. RESULTS: Dimethyl sulfide, toluene, and dodecane obtained of newly-diagnosed APL patients were significantly higher, while ethanol, n-hexanal, and benzaldehyde were significantly lower than those of healthy people (P<0.05). Compared with the newly-diagnosed group, dimethylsulfide, toluene, and dodecane of the remission group significantly decreased, while ethanol, n-hexanal, and benzaldehyde significantly increased (P<0.05), which was just opposite from the relapse group. CONCLUSION Dimethyl sulfide, toluene, dodecane, ethanol, n-hexanal, and benzaldehyde can be used as biomarkers for the diagnosis and prognosis assessment of APL patients.
Exhalation ; Gas Chromatography-Mass Spectrometry ; Granulocyte Precursor Cells ; Humans ; Leukemia, Promyelocytic, Acute/diagnosis* ; Volatile Organic Compounds/analysis*

Neutrophilic leukemoid reaction may occur in many situations, including hemolysis, malignancy, infection, and exposure to certain toxins. It usually shows morphological overlap with chronic myeloid leukemia in which promyelocytes are not majorly associated. Here, we present a case of promyelocytic leukemoid reaction in a patient with sepsis. A 28-year-old man was admitted for renal stone removal. After percutaneous nephrolithotomy, his condition deteriorated with fever (37.8℃), tachycardia (130/min), acute renal failure, pleural effusion, and pulmonary edema. Complete blood count indicated a white blood cell count of 73.39×10⁹/L including 82% promyelocytes, hemoglobin 8.9 g/dL, and platelet count of 85×10⁹/L. A bone marrow aspirate showed that promyelocytes accounted for 73.8% of all nucleated cells. Following bone marrow examination, treatment with all-trans retinoic acid (ATRA) was started immediately. Reverse transcription polymerase chain reaction (RT-PCR) study revealed the absence of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) and other RARA (retinoic acid receptor alpha) rearrangements. Once the chromosome analysis of bone marrow cells demonstrated the normal karyotype, ATRA was discontinued.
Acute Kidney Injury ; Adult ; Blood Cell Count ; Bone Marrow ; Bone Marrow Cells ; Bone Marrow Examination ; Fever ; Granulocyte Precursor Cells ; Hemolysis ; Humans ; Karyotype ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Promyelocytic, Acute ; Leukemoid Reaction* ; Leukocyte Count ; Nephrostomy, Percutaneous ; Neutrophils ; Platelet Count ; Pleural Effusion ; Polymerase Chain Reaction ; Pulmonary Edema ; Reverse Transcription ; Sepsis* ; Tachycardia ; Tretinoin

MPL mutation is an important molecular marker in myeloproliferative neoplasms (MPN). Although MPL W515 is a hot spot for missense mutations in MPN, MPL S505 mutations have been reported in both familial and non-familial MPN. A 72-year-old male visited the hospital, complaining mainly of dizziness and epistaxis. Leukocytosis, anemia, thrombocytopenia, tear drop cells, nucleated RBCs, and myeloblasts were observed in both complete blood cell counts and peripheral blood smears. Bone marrow aspiration failed due to dilution with peripheral blood. BM biopsy indicated hypercellular marrow, megakaryocytic proliferation with atypia, and grade 3 reticulin fibrosis. Conventional cytogenetics results were as follows: 46,XY,del(13)(q12q22)[19]/46,XY[1]. Molecular studies did not detect JAK2 V617F, BCR/ABL translocation, JAK2 exon 12, and CALR exon 9 mutations. The MPL S505N mutation was verified by colony PCR and Sanger sequencing following gene cloning. Based on the above findings, a diagnosis of overt primary myelofibrosis (PMF) was indicated. Mutation studies of buccal and T cells were not conducted. Further, family members were not subjected to mutation studies. Therefore, we were unable to determine whether this mutation was familial or non-familial. Six months after the first visit to the hospital, the patient died due to pneumonia and sepsis. Thrombotic symptoms or major bleeding events did not develop during the survival period following diagnosis of PMF. To the best of our knowledge, this may be the first reported case of PMF with the MPL S505N mutation in Korea.
Aged ; Anemia ; Biopsy ; Blood Cell Count ; Bone Marrow ; Clone Cells ; Cloning, Organism ; Cytogenetics ; Diagnosis ; Dizziness ; Epistaxis ; Exons ; Fibrosis ; Granulocyte Precursor Cells ; Hemorrhage ; Humans ; Korea* ; Leukocytosis ; Male ; Mutation, Missense ; Pneumonia ; Polymerase Chain Reaction ; Primary Myelofibrosis* ; Reticulin ; Sepsis ; T-Lymphocytes ; Tears ; Thrombocytopenia

BACKGROUND: NUP98 has numerous partner genes of which plant homeodomain (PHD) finger protein 23 (PHF23) fusion with NUP98 (NP23) can be detected by RT-PCR in patients with cytogenetically normal acute myelogenous leukemia (AML). In this fusion transcript of NP23 PHD of PHF23 is known to specifically bind H3K4me3 residues and act as a chromatic modifier. Disulfiram (DSF) which inhibits the binding of PHD to H3K4me3 residues selectively killed NP23 myeloblasts in vitro and therefore, we planned to evaluate the efficacy of DSF in vivo. METHODS: Cultured 961C cells (CD45.2), NP23 myeloblast cells were transplanted into B57BL/6 mice (CD45.1). Using limit dilution assay the number of leukemic stem cells (LSCs) could be calculated. A certain amount of 961C cells were transplanted into B57BL/6 mice and DSF was treated after 1 week. The engraftment level was monitored with CD45.2. Kaplan Meier survival curve was used to compare the survival between therapeutic and control group. RESULTS: 961C cells could be transplanted without radiation in recipient mice. Calculated LSC was estimated to be 1 out of 184 cells (95% CI range, 56–609). When treated with DSF of different doses and administration routes in 961C recipient mice no survival advantage of DSF was observed in 961C transplanted immunocompetent mouse, however it was evident that engraftment level was consistent in both groups. CONCLUSION: No survival advantage of DSF in 961C transplanted immunocompetent mouse was observed, however it was evident that 961C cells shared niche with normal hematopoietic stem cells (HSCs). We expect that 961C cells and transplanted recipient mice have the potential to be used as in vivo system for new drugs development as well as for research dealing with niche for normal HSCs and LSCs.
Animals ; Disulfiram ; Fingers ; Granulocyte Precursor Cells ; Hematopoietic Stem Cells* ; Humans ; In Vitro Techniques ; Leukemia, Myeloid, Acute ; Mice ; Plants ; Stem Cells

In patients with acute myeloid leukemia (AML), pleural effusion may be attributed to various factors, including infection, hypoalbuminemia, and renal failure. However, leukemic infiltration of the pleural fluid is rarely reported and poorly understood. Extramedullary diseases have been reported with increasing frequency as the survival rates of patients with AML have increased. However, the reported prognostic effects of leukemic pleural effusion in patients with AML range from none to a worse prognosis. Here, we report a case of acute promyelocytic leukemia (APL) in a patient exhibiting leukemic pleural effusion with fluorescence in situ hybridization (FISH) results indicating the presence of the PML-RARA fusion gene. A 52-year-old man presented with pancytopenia, dyspnea, and fever. He had a medical history of hypertension, end-stage renal disease, and hepatitis B virus-related liver cirrhosis. A peripheral blood smear revealed the presence of multiple abnormally hypergranular promyelocytes. White blood cell differential counts were not performed due to severe pancytopenia. A bone marrow examination, immunophenotyping analysis, and cytogenetic and molecular studies revealed APL. The patient was treated with all-trans retinoic acid immediately after abnormal promyelocytes were observed in the peripheral blood smear, but induction chemotherapy was delayed because of his poor condition. His persistent dyspnea and abdominal discomfort led to a thoracentesis and the observation of abnormal promyelocytes that were positive for PML-RARA fusion gene by FISH. To our knowledge, this is the first report of leukemic pleural infiltration with PML-RARA fusion gene-positivity via FISH.
Bone Marrow Examination ; Cytogenetics ; Dyspnea ; Fever ; Fluorescence ; Granulocyte Precursor Cells ; Hepatitis B ; Humans ; Hypertension ; Hypoalbuminemia ; Immunophenotyping ; In Situ Hybridization ; Induction Chemotherapy ; Kidney Failure, Chronic ; Leukemia, Myeloid, Acute ; Leukemia, Promyelocytic, Acute ; Leukemic Infiltration ; Leukocytes ; Liver Cirrhosis ; Middle Aged ; Pancytopenia ; Pleural Effusion ; Prognosis ; Renal Insufficiency ; Survival Rate ; Thoracentesis ; Tretinoin

OBJECTIVETo study the efficacy and safety of Shuanghuang Shengbai Granule (, SSG), a traditional Chinese herbal medicine, on myelosuppression of cancer patients caused by chemotherapy.

METHODSA total of 330 patients were randomly assigned to the treatment group (220 cases, analysed 209 cases) and the control group (110 cases, analysed 102 cases) with a 2:1 ratio by envelope method. The patients in the treatment group at the first day of chemotherapy started to take SSG for 14 days, while the patients in the control group took Leucogon Tablets. The changes of the blood routine, clinical symptoms and immune function in both groups were observed for safety and efficacy evaluation.

RESULTSAt the 7th day of chemotherapy, the white blood cells (WBCs) level in the treatment group was significantly higher than that in the control group (P<0.05). After treatment, the WBCs rate in the normal range accounted for 50.2% in the treatment group, the myelosuppression of WBCs and neutrophil were mainly grade I, while 8.1% and 5.7% of patients emerged grade III and grade IV myelosuppression, respectively. The incidence of myelosuppression of the treatment group was significantly lower than that of the control group (P<0.05). The total effective rate of Chinese medicine syndrome in the treatment group was significantly higher than that in the control group (84.2% vs. 72.5%, P<0.05). The immune cell levels in both groups were maintained in the normal range. Compared with that before treatment, the levels of CD3and CD4cells were significantly increased in the treatment group after treatment (P<0.05). The discrepancy of CD3and CD4cell activity before and after treatment in both groups were significantly different (P<0.05). No obvious adverse event occurred in both groups.

CONCLUSIONSSG had a protection effect on bone marrow suppression, and alleviated the clinical symptoms together with clinical safety.

Antineoplastic Agents, Phytogenic ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Granulocyte Precursor Cells ; drug effects ; Humans ; Immune Tolerance ; drug effects ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Neoplasms ; drug therapy ; Pancytopenia ; chemically induced ; prevention & control ; Treatment Outcome

OBJECTIVETo investigate the immunophenotype of leukemia promyelocytes (LP) in bone marrow of patients with acute promyelocytic leukemia (APL) and to explore their characteristics and significance.

METHODSThe immunophenotypes of leukemia cells in 43 patients with APL were analyzed by means of 4 color immunophenotypes; the cell population in which CD45 strength localized at 10(2) and the SSC strength locatized at 10(2) was defined as R3, the cell population in which CD45 strength localized at 10(3) and the SSC strength localized at 10(2) was defined as R5, moreover the ratio of positive cells >80% was defined as strong positive expression, the ratio of positive cells between 20%-80% was difined as weak positive expression, the ratio of positive cells <20% was difined as negative by gating method of CD45/SSC.

RESULTSThere was a abnormal cell population (R3) in 79.07% cases; the immunophenotypes of R3 was cheracteried by high SSC, weaker expression of CD45, the rate of CD38, CD9 and CD13 all was 100%, moreover their bright expression (>80%) was 86.05%, 90.70% and 86.05%, respectively; the positive expression rate of CD33, CD117 and CD64 was 97.67%, 95.35% and 83.80% respectively, moreover thier bright expression was 84.04%, 69.77% and 30.23% respectively; the CD15 was weakly expressed in 39.53% cases, the CD34 and HLA-DR were weakly expression in 16.28% and 6.98% cases respectively. All the cases did not express CD116. There were 2 cell populations (R3 and R5) in 20.93% cases, the immunophenotypic features of R3 were cosistant with above mentioning, while the immunophenotypes of R5 were lower than those of R3 SSC; the fluorescence intensity of CD45 was higher, but lower than that in normal lymphycytes, the positive rate of CD9, CD13, MPO was 100%, moreover thier fluorescence intensity was high; they did not expressed CD123, CD25, CD22, CD4, CD64 and CD14. Thereby it can be concluded that the typical immunophenotypes is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-) in APL. There was a special immunophenotype in the APL with basophilic granules. Conclusoin: APL has a characteristic immunophenotypic profile, whose typical immunophenotype is characterized by CD13(+) CD9(+) CD38(+) CD33(+) CD117(+) CD64(+) CD11b(-) CD34(-) HLA-DR(-). The special immunophenotype exists in the APL with basophilic granules. Flow cytometric immunophenotyping may be a useful for rapid recognition of APL and has significant for prognosis.

Antigens, CD ; metabolism ; Cell Count ; Flow Cytometry ; Granulocyte Precursor Cells ; classification ; HLA-DR Antigens ; metabolism ; Humans ; Immunophenotyping ; Leukemia, Promyelocytic, Acute ; classification ; immunology ; Leukocyte Common Antigens ; metabolism ; Prognosis

OBJECTIVETo investigate the effects of oxygen concentration and reactive oxygen species (ROS) on the biological characteristics of hematopoietic stem cells (HSC) and to analyzed the relationship among the oxygen concentration, ROS and the biological characteristics of mouse HSC through simulation of oxygen environment experienced by PB HSC during transplantation.

METHODSThe detection of reactive oxygen species (ROS), in vitro amplification, directional differentiation (BFU-E, CFU-GM, CFU-Mix), homing of adhesion molecules (CXCR4, CD44, VLA4, VLA5, P-selectin), migration rate, CFU-S of NOD/SCID mice irradiated with sublethal dose were performed to study the effect of oxgen concentration and reactive oxygen species on the biological characteristics of mouse BM-HSC and the relationship among them.

RESULTSThe oxygen concentrations lower than normal oxygen concentration (especially hypoxic oxygen environment) could reduce ROS level and amplify more Lin(-) c-kit(+) Sca-1(+) BM HSC, which was more helpful to the growth of various colonies (BFU-E, CFU-GM, CFU-Mix) and to maintain the migratory ability of HSC, thus promoting CFU-S growth significantly after the transplantation of HSC in NOD/SCID mice irradiated by a sublethal dose. BM HSC exposed to oxygen environments of normal, inconstant oxygen level and strenuously thanging of oxygen concentration could result in higher level of ROS, at the same time, the above-mentioned features and functional indicators were relatively lower.

CONCLUSIONThe ROS levels of BM HSC in PB HSCT are closely related to the concentrations and stability of oxygen surrounding the cells. High oxygen concentration results in an high level of ROS, which is not helpful to maintain the biological characteristics of BM HSC. Before transplantation and in vitro amplification, the application of antioxidancs and constant oxygen level environments may be beneficial for transplantation of BMMSC.

Animals ; Cell Differentiation ; Culture Media ; chemistry ; Erythroid Precursor Cells ; cytology ; Granulocyte-Macrophage Progenitor Cells ; cytology ; Hematopoietic Stem Cells ; cytology ; metabolism ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Oxygen ; chemistry ; Reactive Oxygen Species ; metabolism

Myeloid sarcoma (MS) is an extramedullary involvement of immature myeloid proliferation. An isolated MS is defined as a myeloblastic tumor when it arises without any concomitant circulating disease. A diagnosis of MS is established using pathologic features including infiltration of myeloblasts and strong myeloperoxidase expression with negative cytokeratin immunohistochemical staining. We report a rare case of colonic MS without any peripheral blood abnormality. If the affected patient were left untreated, the MS could evolve into acute myeloid leukemia (AML) within one year. Several studies recommend the same regimens of chemotherapy as used for circulating AML to treat isolated MS. We focused on the diagnosis of MS in this study. The correct diagnosis of MS is important for adequate treatment. In conclusion, MS should be considered in the differential diagnosis of intestinal tumor.
Colon ; Colonic Neoplasms ; Diagnosis ; Diagnosis, Differential ; Drug Therapy ; Granulocyte Precursor Cells ; Humans ; Intestines* ; Keratins ; Leukemia, Myeloid, Acute ; Peroxidase ; Sarcoma, Myeloid*