Recent Advances of Researches on Expression, Function and Regulation of CD22 / 中国实验血液学杂志

CD22 is a type I transmembrane protein expressed on most mature B lymphocyte, and plays a significant role in signal transduction pathways. CD22 acts as a co-receptor of the B-cell receptor (BCR) that inhibits the BCR signaling by antigen-receptor interaction. The phosphorylation of CD22 can be triggered by cross-linking of CD22 with the BCR through antigen, then predominantly triggers the dephosphorylation and inactivation of downstream proteins and inhibit the BCR signaling. Autoimmune disease could be caused by the abnormal expression or dysfunction of CD22 which interrupts BCR signaling and then influences the quantity and function of B cells. The further study of the function and regulation of CD22 would help us understanding the pathogenesis of autoimmune disease and setting theoretical basis for its targeting treatment. In this article, the structure and expression of CD22, the ligands of CD22, the regulation of BCR and transmenbrane signaling, the effect of CD22 on B cells, and CD22 and autoimmune diseases were reviewed.

Characteristics of 4 specific target antigens in adult acute lymphoblastic leukemia / 中国实验血液学杂志

This study was aimed to investigate clinical and prognostic significances of 4 target antigens (CD19, CD20, CD22 and CD33) for antibody-based immunotherapy and to evaluate the applications of these antibody-based target therapy to adult acute lymphoblastic leukemia (ALL). The immunophenotype of 220 adult patients with ALL were analyzed by four-color flow Cytometry, and cytogenetic and molecular parameters were detected by conventional cytogenetics, fluorescence in situ hybridization, real-time quantitative PCR, nested PCR and DNA sequencing. The results showed that CD19 positive (CD19(+)) cases were more in female (46.4% vs. 23.4%, P = 0.006), elderly patients aged > 60 years (14.4% vs. 2.1%, P = 0.022), CD33(+) co-expression cases (47.8% vs. 12.0%, P = 0.001) and genetic high-risk group (55.8% vs. 20.8%, P = 0.002) compared with CD19 negative (CD19(-)) cases; CD20(+) cases had lower co-expression of CD13 than CD20(-) cases (31.6% vs.67.1%, P = 0.000) and no significant prognostic indications for CD20(+) was observed; CD22(+) cases had higher relapse rate at 12-month than CD22(-) cases (93.9% vs.57.1%, P = 0.041) in B-ALL patients; CD33(+) cases had higher incidence of Ph(+) than CD33(-) cases (43.5% vs.19.4%, P = 0.007) and significantly correlated with Ph(+) (r = 0.261, P = 0.006). It is concluded that elucidation of the characteristics of the target antigens (CD19, CD20, CD22, CD33) used for antibody-based immunotherapy will help hematologists making the correct decision whether and when to use these antibody-based target therapies.

Immunotherapy of non-Hodgkin's lymphomas (NHL) by anti-CD22 antibody--review / 中国实验血液学杂志

CD22 is a transmembrane sialoglycoprotein and a member of the immunoglobulin superfamily. Its expression is restricted to the B cell lineage and a vast majority of B cell NHLs. CD22 plays a key role in B cell development, survival, and function. Humanized anti-CD22 antibodies were developed to minimize the immunogenicity and to enhance effector interactions during their developments of diagnostic and immunotherapeutic agent. Preclinical test with anti-CD22 antibodies indicates that a single, conjugated or radiolabeled agent has shown preliminary antitumor activity in patients with recurrent and heavily pretreated NHL. Anti-CD22 antibodies were well tolerated, without dose-dependant toxicity. Anti-CD22 antibodies are currently being evaluated in combination with rituximab, and the early results suggest that the combination of the two antibodies are well tolerated and may result in better clinical activity than the single agent alone. Thus, anti-CD22 antibodies are theoretically good candidates alone and in combination with other drugs in the treatment of B cell malignancies. In this review, the physiologic function and characteristics of CD22 antigen as target molecule of guide therapy for NHL, the types of anti-CD22 antibodies in therapy of NHL and the combination use with other antibodies were summarized.

Abnormal expression of cCD79a/cCD22 in acute myeloid leukemia with t (8;21) / 中华血液学杂志

<p><b>OBJECTIVE</b>To report abnormal expression of cCD79a/cCD22 in four cases of acute myeloid leukemia (AML) with t (8;21).</p><p><b>METHODS</b>The characteristics of morphology, immunophenotype, chromosome karyotype (MIC) and clinical manifestations of 4 AML patients with t (8;21) expressing cCD79a/cCD22 were analyzed.</p><p><b>RESULTS</b>The features of the 4 patients were: (1) no difference in gender; (2) young age; (3) exmedullary infiltration may be present; (4) normal number of white blood cells in peripheral blood; (5) morphology showed acute myeloid leukemia with high percentage of blast cells; (6) B-lymphoid and myeloid immunophenotype, and high expression of CD34; (7) frequent depletion of Y chromosome and complex changes of chromosomes; (8) positive for AML1/ETO fusion gene; (9) response well to chemotherapy regimen which simultaneously treated myeloid and lymphocytic leukemia.</p><p><b>CONCLUSION</b>Abnormal expression of cCD79a/cCD22 in AML with t (8;21) (q22;q22) suggested that this kind of leukemia might be related with abnormal expression gene of B cell.</p>

Biological characteristics of hyperleukocytic acute leukemia / 中国实验血液学杂志

The study was to investigate the biological characteristics of hyperleucocyte acute leukemia (HAL) and its clinical significance. Immunophenotyping was performed in 48 HAL patients and 73 NHAL patients by three-color flow cytometry analysis using CD45/SSC gating, meanwhile the cytogenetic analysis was performed in 74 patients. The results showed that as compared with NHAL group, HAL group had lower proportion of eryth-lineage in bone marrow (P < 0.05); in AML, the CD14 expression of HAL group was apparently higher than that of NHAL group (P < 0.05); in ALL, HAL group had higher expression of CD8 and lower expression of CD22, cCD79a compared with NHAL group (P < 0.05); the two groups had no significant difference in expression of special lineage antigens and overlapping lineage antigens (P > 0.05). The CR rate of HAL group was lower than that of NHAL group. It is concluded that bone marrow inhibition of HAL group is more severe than that of NHAL group. In AML, monocytic leukemia is easier to become into HAL than other leukemias. In ALL, T-lineage antigens of HAL group are more easily expressed than those of NHAL group; the leukemia cells of HAL group are naiver than those of NHAL group, meanwhile the prognosis of HAL is poor.

Establishment of cytokine-independent human myelodysplastic cell line and its characteristics / 中国实验血液学杂志

This study was aimed to establish a cytokine-independent human myelodysplastic cells line from bone marrow of a patient with MDS-CMML. This cell line was incubated in mixed culture of RPMI 1640 and DMEM with 15% bovine serum, but without cytokines; its biological characteristics were identified by morphology, surface marker profiles, cell proliferation, differentiation and apoptosis. The results showed that the established cell line could not depend on cytokines for long-term survival and growth, and could differentiate into colony-forming unit-macrophage, colony-forming unit-megakaryocyte. In conclusion, a cytokine-independent human myelodysplastic syndrome cell line, named MDS-JSN04 (MDS Nanjing Jiansu 04), was established. Its partial biological characteristics were identified and clarified.

Sensitivity and specificity analysis of the lineage related antibodies in acute leukemia immunophenotyping by flow cytometry / 中国实验血液学杂志

To evaluate the sensitivity and specificity analysis of the lineage related antibodies in acute leukemia immunophenotyping by flow cytometry (FCM), immunophenotyping in 184 patients with acute leukemia was performed by FCM analysis. The results showed that in the lineage-related antibodies of acute myelocytic leukemia (AML), the sensitivity of CD13 and CD33 was higher (95.5% and 91.2%, respectively), the specificity of them was deficient (72.5% and 62.2%, respectively); the sensitivity of MPO was low (69.1%), but the specificity was high (100%); the sensitivity and specificity of CD117 were high (88.2% and 100%, respectively); the sensitivity of CD14 and CD15 was low (18.4% and 27.2%, respectively); the specificity of CD14 with monocytes was high. As the lineage-related antibodies of B-lineage ALL were concerned, CD19 showed high sensitivity and low specificity (100% vs 83.4%); the sensitivity and specificity of CD79a (96.4% vs 100%) and CD22 (100% vs 100%) were high; the sensitivity and specificity of CD10 (53.6% vs 82.5%) and CD20 (70.4% vs 87.5%) were low. In T-lineage ALL, the specificity of CD3 was high (97.5%), but the sensitivity was below the mark (80.0%); the sensitivity of CD7 was high (100%), but the specificity was low (77.9%); while the sensitivity and specificity of CD5, CD2 and CD1a were all deficient. In conclusion, the sensitivity and specificity analysis of the lineage-related antibodies in acute leukemia immunophenotyping are coincident with St Jude immunophenotyping project. It seems only that CD117 is superior to MPO in defining AML, but the sensitivity and specificity analysis of CD22 and CD79 are similar in defining B-lineage ALL, therefore, anyone of them may be selected as your need.

Comparative study of expressions of cytoplasmic CD79a and other B-lymphoid immunomarkers in acute leukemic cells / 中国实验血液学杂志

To evaluate the expression of cytoplasmic CD79a (CyCD79a) and other commonly used B-lymphoid immunomarkers including cytoplasmic CD22 (CyCD22), CD19, CD20 and CD10 in various acute leukemia cells and to define the most sensitive and specific markers in the diagnosis of precursor B-cell acute lymphoblastic leukemia (pB-ALL), the immunophenotypic data from 221 de novo adult and pediatric acute leukemia patients as studied using multi-parameter flow cytometry in addition to routine morphologic and enzyme cytochemical assay, were retrospectively analyzed. Cytogenetic and/or molecular biological data in all 45 cases of acute promyelocytic leukemia (APL) and 13 cases of acute leukemia suspected as AML with the fusion genes such as AML1/ETO and CBFbeta/MYH11 were investigated. The results showed that CyCD79a and CyCD22 were the most sensitive and specific markers respectively for pB-ALL. Expression of CyCD79a was seen in 100% of 58 cases of pB-ALL. At the same time, none (0%) of all 147 cases of acute myeloid leukemia (AML) and 15 cases of precursor T-cell acute leukemia (pT-ALL) was positive for CyCD22. The conclusion is made that united detection of CyCD79a and CyCD22 is the optimal immune combination for the diagnosis pB-ALL and the distinguishing pB-ALL with AML and pT-ALL.

Detection of cytoplasmic antigens by flow cytometry and its implication for leukemia immunophenotyping / 中国实验血液学杂志

The purpose of this study was to optimize a fixation procedure for detection of cytoplasmic antigens by flow cytometry(FCM) and to evaluate the effect of intracellular CD3, CD22, CD79a and myeloperoxidase(MPO) in lineage assignment. Four kinds of fixation procedure and three or four color direct immunofluorescence staining were used to permeate cell membrane and label cell surface and intracellular antigens by means of FCM. Results showed that percentage of cytoplasmic antigens positive cells was the highest and cell scatter and fluorescence intensity of CD45 were not changed after using of FACS permeabilization solution. MPO protein was positive in 16/18 acute myeloid leukemia(AML) patients. 4 cases of T cell-acute lymphoblastic leukemia (T-ALL) cases were positive for cytoplasmic CD3(c CD3) but surface CD3 was negative. c CD22 was only detected in 9/13 of B-ALL and cCD79a was positive in 5/5 B-ALL. 18/38 cases of acute leukemia were expressed in more than one lineage marker, 8/21 cases of acute non-lymphocytic leukemia(ANLL) were CD7 positive. 7/17 cases of acute lymphocytic leukemia (ALL) expressed CD13. After further cytoplasmic antigen detection, one was considered to be a T/myeloid biphenotypic leukemia, another one was diagnosed as biclonal or mixed leukemia. The results suggest that intracellular CD3,CD22,CD79a and MPO are lineage specific markers, they are very important for biphenotypic and biclonal/mixed acute leukemia identification