Study of single nucleotide polymorphism of SOCS gene in typical myeloproliferative neoplasms / 中国实验血液学杂志

This study was purposed to investigate the effect of mutation and single nucleotide polymorphism (SNP) of suppressor of cytokine signaling (SOCS) on the typical myeloproliferative neoplasms (MPN) and its mechanism. The mutation and SNP of SOCS1, SOCS2, SOCS3 genes in 100 MPN patients were detected by RT-PCR and direct sequencing. The results showed that among 100 cases there were 21 cases with A→C polymorphism in the 63th site nucleotide of the 15 SOCS3 exon (SNP library no reported), 18 cases with A→C polymorphism in the 1779th site nucleotide of the 15 SOCS3 exon, 49 cases with A→G polymorphism in the 2249th site nucleotide of the 15 SOCS3 exon (SNP library no reported), 39 cases with T→C polymorphism in the 2366th site nucleotide of the 15 SOCS3 exon (SNP library no reported), 9 cases with T→C polymorphism in the exon of 15 SOCS2 gene (SNP library no reported). SOCS3 SNP was found in patients with significantly advanced age at diagnosis, the leukocyte count and platelet level were higher than those in patients with wild type, JAK2V617 mutations was found in 87.65% SOCS3 SNP. It is concluded that the SOCS may be an important target for anticancer therapy, the single nucleotide polymorphism of SOCS may involve to pathogenesis of MPN.

Enhanced cytotoxicity against leukemia cells of natural Killer cells from cord blood after expansion in vitro / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the enhanced cytotoxicity against leukemia cells of natural Killer (NK) cells from cord blood (CB) after expansion in vitro.</p><p><b>METHODS</b>NK cells was expanded on a layer of trophoblast cells with irradiated K562-mb15-41BBL cell line for 21 days. The levels of receptors on NK cells were detected by flow cytometry. Cytotoxicity of expanded NK cells against leukemia cells and specific ligand of immunoglobulin like(Ig- liKe)receptors were assessed using 51Cr released assay.</p><p><b>RESULTS</b>There were no differences of inhibitory receptors expression between fresh NK cells and expanded NK cells [CD158a:(16.77±11.65)% vs(14.37±11.12)%, P>0.05; CD158b: (42.48±18.11)% vs (40.92±19.02)%, P>0.05; NKG2A: (70.20±18.43)% vs (78.90±13.69)%, P>0.05], but higher activated receptors expression on expanded NK cells [NKp30: (54.10±13.27)% vs (4.14±2.05)%, P<0.05; NKp44: (72.10±17.30)% vs (0.52±1.16)%, P<0.05; NKp46: (80.63±14.01)% vs (44.19±6.19)%, P<0.05; NKG2D: (97.50±2.55)% vs (72.25±14.35)%, P<0.05]. Expanded NK cells showed higher cytotoxicity against leuKemia cell lines than fresh NK cells [K562: (74.3±3.6)% vs (55.3±4.2)%, P<0.05; Raji: (60.6±5.0)% vs (12.0±3.6)%, P<0.05]. CD158a⁻ CD158b⁻ NK cells had higher cytotoxicity on four types of target cells, but CD158a⁺CD158b⁻ CB-NK cell had lower cytotoxicity on 221-Cw4 and 221-Cw3Cw4 cells. CD158a⁻ CD158b⁺ CB- NK cells had lower cytotoxicity on 221-Cw3 and 221-Cw3Cw4, but CD158a⁺CD158b⁺ CB-NK cells had higher cytotoxicity on 721- 221 cells.</p><p><b>CONCLUSION</b>Expression of activated receptors of expanded NK cells were up-regulated, but no changes of inhibitory receptors. Expanded NK cells showed high cytotoxicity against leukemia cells and kept the specificity of ligand of Ig-like receptors, which could be beneficial to cell-therapy for tumor.</p>

Prognostic value of t(11; 18) (q21; q21) for gastric mucosa-associated lymphoid tissue lymphoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the prognostic value of t(11; 18) (q21; q21) in gastric mucosa-associated lymphoid tissue lymphoma.</p><p><b>METHODS</b>A cohort of thirty-six gastric mucosa-associated lymphoid tissue lymphoma patients who were pathologically identify diagnosis from January 1994 to June 2004 were followed up retrospectively and studied using fluorescence in situ hybridization(FISH) technique to detect t(11; 18) (q21; q21) chromosomal translocation on preservative paraffin specimen.</p><p><b>RESULTS</b>Among thirty-six patients, fifteen (41.67%) were positive for t (11; 18) (q21; q21). All but one were followed up to March 2010, general median survival time (MST) was 87 months. The MST were 43 and 130 months for t(11; 18) positive and negative patients, respectively. The MST between these two groups was notably different (chi-square=29.57, P< 0.01).</p><p><b>CONCLUSION</b>t(11; 18) (q21; q21) is important prognostic factor for gastric mucosa-associated lymphoid tissue lymphoma.</p>

Clinical and cytogenetic analyses of 45 adult patients with acute lymphoblastic leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the correlation between clinical features and cytogenetic finding of 45 adult patients with acute lymphoblastic leukemia (ALL), and to assess the value of chromosomal examination for the diagnosis and prognosis.</p><p><b>METHODS</b>Fluorescence in situ hybridization (FISH) was utilized for detecting the BCR/ABL fusion gene and P53 gene. Median survival time (MST) of patients was compared using Log-rank test.</p><p><b>RESULTS</b>Respectively, the MST of patients with white blood cell count (WBC) ≤30 × 10(9)/L, normal karyotype, or without a Philadelphia chromosome were significantly greater than those with WBC > 30 × 10(9)/L, abnormal karyotype or Philadelphia chromosome (P< 0.05).</p><p><b>CONCLUSION</b>WBC, karyotype abnormalities and presence of Philadelphia chromosome are independent factors for the prognosis of ALL in adult patients.</p>

Abnormal expression of hematopoietic regulatory factors in newly diagnosed patients with acute myeloid leukemia / 中国实验血液学杂志

The aim of this study was to detect the expressions of transforming growth factor (TGFβ(1)), tumor necrosis factor alpha (TNFα) and leukemia inhibitory factor (LIF) in newly diagnosed patients with acute myeloid leukemia (AML) and investigate the association between serum levels of various cytokines and clinical outcomes. The levels of TGFβ1, TNFα and LIF in patient's plasma were detected by enzyme-linked immunosorbent assays (ELISA) and were compared with healthy controls; bone marrow cell morphology, immunology, cytogenetics examinations (MIC) were performed meanwhile. The results showed that levels of TGFβ1, TNFα and LIF were elevated in AML patients as compared with the controls (13.08±9.77 ng/ml, 10.67±15.11 pg/ml, 4.23±4.73 pg/ml vs 8.23±3.12 ng/ml, 5.86±3.05 pg/ml, 2.78±1.22 pg/ml) (p all<0.05). The three cytokines and MIC examination analysis indicated that level of LIF was abnormally elevated in M5 patients (7.14±6.62 pg/ml); TNFα was abnormally elevated in M4 and M3 patients especially M4; TGFβ1 level in M6 and M2 patients was higher than others. TGFβ1 plasma concentration in low-risk group the lowest (10.45±4.73 ng/ml), and that in middle risk group was the highest (16.13±13.76 ng/ml) (p<0.05); the levels of other two kinds of factors in the chromosome karyotype groups showed no significant difference. It is concluded that TGFβ1, TNFα and LIF expressions showed increased level in the untreated patients with de novo AML, the TGFβ1 level among which is associated with the prognosis of patients.

Expression of soluble GM-CSF-Ralpha in patients with acute myeloid leukemia / 中国实验血液学杂志

To evaluate soluble GM-CSF-Ralpha expression in patients with acute myeloid leukemia (AML) and its clinic significance, plasma concentration of solGM-Ralpha in de novo 66 patients with AML was detected by enzyme-linked immuno-sorbent assay, and the relationship between solGM-Ralpha levels and various clinical parameters was analyzed. The result showed that the levels of solGM-Ralpha in plasma of patients with AML were significantly higher than that in plasma of normal controls; the lowest level of solGM-Ralpha was found in plasma of patients with AML-M3 (3897.75 +/- 2651.43 pg/ml), the highest level of solGM-Ralpha was observed in plasma of patients with AML-M5 (9990.92 +/- 6325.43 pg/ml). Patients with high level of solGM-Ralpha were generally accompanied with a distinct clinical picture, including higher counts of white blood cell and myeloid precursors, as well as higher expression of CD34, CD95 and CD116 antigen. It is concluded that the high level of solGM-Ralpha in plasma of patients may suggest AML poor prognosis and play a role in pathogenesis of leukemia, the GM-CSF and its receptor solGM-Ralpha needs further study.