Huaquan Wang

CD47 is expressed abnormally on hematopoietic cells in myelodysplastic syndrome

The increased LSC in MDS has correlation with the progression to AML, which the mechanism of immune evasion is unclear. Our study showed the expression of CD47 on LSC of the patients in high-risk MDS based on IPSS/WPSS score was higher than that of in low-risk MDS and controls. The level of CD47 on erythroblast of MDS patients had a significant positive correlation with their peripheral RBC count. It suggested that the proportion of CD34(+)CD38(-)CD47(+) cells increased in high-risk MDS which might protect LSC from avoiding phagocytosis, and low-expression of CD47 on erythroblast in MDS might be correlated to anemia.

Effect of DLK1 on tumorigenesis in CD34(+)CD38(-) bone marrow cells in myelodysplastic syndromes.

The myelodysplastic syndromes (MDSs) are a group of clonal stem cell disorders resulting from aberrations within hematopoietic stem cells (HSCs), which may lead to the onset of a number of diseases, including acute myeloid leukemia (AML). Recent studies have demonstrated that the expression levels of the DLK1 gene are increased in MDS. In order to determine whether the addition of DLK1 affects tumorigenesis, small interfering (si)RNAs were designed to target DLK1 in order to knockdown its expression in CD34+CD38− bone marrow cells in MDS. A lower proliferative rate was observed in the CD34+CD38− bone marrow cells following this knockdown of DLK1 expression. The suppression of DLK1 expression resulted in a less aggressive MDS phenotype, which suggests that the upregulation of DLK1 expression may play an oncogenic role in CD34+CD38− bone marrow cells.

Abnormalities of quantities and functions of linker for activations of T cells in severe aplastic anemia

Severe aplastic anemia (SAA) is a rare immune‐regulated disease characterized by severe pancytopenia and bone marrow failure, caused by destruction of hematopoietic cells by the activated T lymphocytes. Linker for activation of T cells (LAT), a transmembrane adaptor protein, plays a key role in T‐cell and mast cell functions. However, it remains unclear how LAT may change in patients with SAA. This study aims at understanding the role of lymphocyte LAT in SAA.

Differential expression of the proteome of myeloid dendritic cells in severe aplastic anemia

Severe aplastic anemia (SAA) is a syndrome of severe bone marrow failure with high mortality. Our previous studies have demonstrated that both immature and activated DC1 increased in the bone marrow of SAA patients, and the balance of DC1 subsets shifted the stable form to active one, which might promote Th0 cells to polarize to Th1 cells and cause the over-function of T lymphocytes and hematopoiesis failure in SAA. So we assumed myeloid dendritic cells (mDCs) may be the key immune cells that cause destruction of hematopoietic cells in SAA, but the mechanism of activation of mDCs is unclear. Here, we investigated the proteome of mDCs in SAA patients to further explore the pathogenesis of SAA and the possible antigen that leads to immune activation in SAA. mDCs from 12 SAA patients, 12 remission patients and 12 controls were sorted by flow cytometry and examined by two-dimensional gel electrophoresis and mass spectrometry. Intensity changes of 41 spots were detected with statistical significance. Nine of the 41 spots were identified by MALDI-TOF/TOF tandem mass spectrometry. Changes in protein expression levels were found in the SAA group. These changes reveal that abnormal expression of cofilin, glucose-6-phosphate dehydrogenase and pyruvate kinase enzyme M2 in mDCs from SAA patients may be the reason for mDC hyperfunction.

TET2 Expression in Bone Marrow Mononuclear Cells of Patients with Myelodysplastic Syndromes and Its Clinical Significances

Objective To investigate the expression of TET2 mRNA and protein in the bone marrow mononuclear cells (BMMNC) of patients with myelodysplastic syndrome (MDS) and its clinical significance. Methods The expression of TET2 mRNA and protein in bone marrow mononuclear cells (BMMNC) of 32 patients with MDS and 20 healthy donors was examined by qPCR and Western blot. Results The expression of TET2 mRNA in BMMNC was down-regulated in MDS patients compared with the donor group [(0.41±0.28)% vs. (1.07±0.56)%] (P<0.001). Compared with lower expression group (TET2<0.4) [(6.53±6.17)%], patients with higher expression of TET2 (≥0.4) presented significantly lower proportion of bone marrow blasts [(1.21±1.56)%] (P<0.05). The expression of TET2 mRNA in BMMNC of MDS patients was inversely correlated with malignant clone burden (r=-0.398, P<0.05) and IPSS (r=-0.412, P<0.05). The expression of TET2 protein was down-regulated in MDS patients compared with that in the donor group. Conclusions The mRNA and protein expression of TET2 in BMMNC of MDS patients is decreased, which might be useful as an important parameter for the evaluation of MDS clone burden.

Recombinant Human Thrombopoietin Treatment Promotes Hematopoiesis Recovery in Patients with Severe Aplastic Anemia Receiving Immunosuppressive Therapy

Objective. To assess the effectiveness of recombinant human thrombopoietin (rhTPO) in severe aplastic anemia (SAA) patients receiving immunosuppressive therapy (IST). Methods. Eighty-eight SAA patients receiving IST from January 2007 to December 2012 were included in this retrospective analysis. Of these, 40 subjects received rhTPO treatment (15000u2009U, subcutaneously, three times a week). rhTPO treatment was discontinued when the platelet count returned to normal range. Hematologic response, bone marrow megakaryocyte recovery, and time to transfusion independence were compared. Results. Hematologic response was achieved in 42.5%, 62.5%, and 67.5% of patients receiving rhTPO and 22.9%, 41.6%, and 47.9% of patients not receiving rhTPO at 3, 6, and 9 months after treatment, respectively (P = 0.0665, P = 0.0579, and P = 0.0847, resp.). Subjects receiving rhTPO presented an elevated number of megakaryocytes at 3, 6, and 9 months when compared with those without treatment (P = 0.025, P = 0.021, and P = 0.011, resp.). The time to platelet and red blood cell transfusion independence was shorter in patients who received rhTPO than in those without rhTPO treatment. Overall survival rate presented no differences between the two groups. Conclusion. rhTPO could improve hematologic response and promote bone marrow recovery in SAA patients receiving IST.

Expression of DLK1 Gene in the Bone Marrow Cells of Patients with Myelodysplastic Syndromes and Its Clinical Significance

Objective This study aims to investigate the expression of delta-like 1 (DLK1) gene in the bone marrow cells of patients with myelodysplastic syndromes (MDS) and to explore its molecular characteristics for the early diagnosis of MDS. Methods The expression of DLK1 mRNA in the bone marrow cells of cases with MDS, acute myeloid leukemia (AML), and normal control groups were measured by real-time polymerase chain reaction and were analyzed for clinical significance. Results Significantly higher expression of DLK1 mRNA was observed in the bone marrow cells of MDS patients (0.7342±0.3652) compared with the normal control group (0.4801±0.1759) (P<0.05). The expression of DLK1 mRNA had a positive correlation with the proportion of bone marrow blasts (r=0.467, P<0.05). Moreover, DLK1 mRNA expression was significantly increased as MDS progressed (P<0.05). Patients with abnormal karyotypes exhibited significantly higher expression of DLK1 mRNA (0.9007±0.4334) than those with normal karyotypes (0.6411±0.2630) (P<0.05). Subsequently, patients with highly expressed DLK1 (≥0.8) presented significantly higher malignant clone burden (0.4134±0.3999) than those with lower DLK1 expression (<0.8),(0.1517±0.3109), (P<0.05). Conclusions The DLK1 gene was highly expressed in MDS patients, and was increased as MDS progressed. The expression of DLK1 mRNA was positively correlated with the proportion of the bone marrow blasts. A high expression of DLK1 gene suggested a higher malignant clone burden of MDS.

Lung papillary adenocarcinoma complicated with paraneoplastic autoimmune hemolytic anemia: A case report

A middle‐aged woman presented at our facility and was diagnosed after surgery with lung papillary adenocarcinoma. Seven years earlier, she had suffered from autoimmune hemolytic anemia (AIHA), which was refractory. Following lung surgery, the AIHA was cured.

A case of lung cancer with first signs of hematological manifestations

A 48-year-old man presented with a one-week history of palpitation, fatigue, and epistaxis. Streaky hemoptysis occurred occasionally, and decreased muscular strength of the left extremities was found. The cranial computer tomography (CT) taken at a local hospital indicated infarction of the right basal ganglia and temporoparietal lobe. Physical examination found T37.5°C, HR112bpm, Bp120/80 mmHg, and R20bpm. The patient looked pale, with petechia on the lower limbs. The muscular strength of the left extremities was grade IV, with positive Babinski signs on both sides. A routine blood test showed decreased counts of hemoglobin (81 g/L) and platelets (13 ¥ 10/L). Coagulation function showed an increased level of D-Dimer and a decreased level of fibrinogen. An electrolytes test indicated hypercalcemia. The liver function examination indicated elevated levels of aminotransferases. Urine routine was normal, while fecal occult blood test was positive. Bone marrow puncture was performed in order to find the cause of cytopenia. A hypoplastic marrow was indicated with a decreased ratio of granulocytic series and normal percentage of erythroid series. Platelet counts were decreased and no megakaryocytes were seen. Piles of irregular shaped cells were seen throughout the smear, especially at the end of the smear. The piled cells were in different sizes with round or irregular nuclei, coarse chromatin, obscure nucleoli, and dusty blue cytoplasm with vacuoles. Peripheral blood smear showed decreased granulocytes with immature cells occasionally seen. Thirty erythroblasts were counted among a hundred white blood cells. The impression diagnosis of marrow smear was: (i) marrow metastasis of extramedullary neoplasms; and (ii) lymphoma to be excluded (see Fig 1). Further examinations were performed to seek the existence of primary tumors. Chest CT showed soft tissue density shadow in the area of the right hilus pulmonis. Parts of the bronchi became narrow. Patchy consolidation shadow was seen at the dorsal segment of the inferior lobe of right lung, and interstitial lung markings were increased. Multiple mediastinal lymph nodes were markedly enlarged, and low-density focuses were seen in the liver (see Fig 2). Tumor markers were subsequently detected showing elevated levels of carbohydrate antigen 19-9, neurons enolase enzymes and cell keratin 19 pieces. As a result of these laboratory findings, a diagnosis of small cell lung cancer (SCLC) with bone marrow metastatic tumor was made. The patient refused chemotherapy, therefore, supportive treatments were given. However, the patient failed to respond well to platelet transfusion, and the platelet count ranged between 7 ¥ 10/L and 10 ¥ 10/L. Hemorrhage symptoms were aggravated. He suffered from continuous low fever and ache all over. Finally the patient abandoned treatment and died two weeks later. Cancer patients, especially those in late stage, may display various hematological manifestations, such as cytopenia and coagulation dysfunction. Mechanisms of cytopenia include deficiency of hematopoietic raw materials, marrow infiltration of tumor cells, anemia of chronic disease, microangiopathic hemolytic anemia, bone marrow fibrosis, and inhibited hematopoiesis as a result of chemotherapy. Thrombophilia presented by cancer patients is considered to be associated with abnormal blood flow, impaired vascular integrity, and changes of blood components. Li Xiao et al. analyzed bone marrow biopsies of 10112 patients with hematological diseases, and found 101 of them (about 1%) were marrow metastasis of non-hematological tumors, among which lung cancer was most frequently seen. The patient in this case presented with a right pulmonary hilar mass with elevated neurons enolase enzymes, which supported the diagnosis of SCLC. The piles of irregular shaped cells in the marrow smear, as well as the resulting cytopenia, were typical signs of marrow infiltration of extramedullary neoplasms. Primary bronchogenic carcinoma (abbr. lung cancer) is one of the most commonly seen malignant tumors. Small cell lung cancer (SCLC) accounts for 15–20% of lung cancers, and displays a higher tendency of marrow metastasis in its early Correspondence Zonghong Shao, Hematology Department, General Hospital, Tianjin Medical University, 154 Anshandao, Tianjin 300052, China. Tel: +86 2260362085 Fax: +86 2260362086 E-mail: shaozonghong@sina.com