Aplastic anemia with macrocytic anemia: a study based on long-term follow-up / 中华血液学杂志

<p><b>OBJECTIVE</b>To elucidate the clinical features, response rate, prognosis and clonal evolution of aplastic anemia (AA) with macrocytic anemia (mAA).</p><p><b>METHODS</b>The clinical features at initial diagnosis and data in follow up of mAA hospitalized from January 2000 to October 2011 were analyzed retrospectively.</p><p><b>RESULTS</b>(1) Of 153/568 (26.9%) cases of mAA at initial diagnosis, 114(74.5%)were non-severe AA (NSAA), 39(25.5%)severe AA (SAA) and 0 very severe AA (VSAA), while the proportion was 16.2%, 45.2%, and 38.6% in 376 normocytic anemia AA (nAA), and the difference is statistically significant(χ(2) = 181.390; P = 0.000). The median age of mAA was significantly higher than that of nAA \[30(4 - 70)years vs 19 (3 - 68) years, P = 0.001\]. (2) There were no statistical difference in hemoglobin, absolute neutrophil count (ANC), platelet count (PLT), response rate after 6 months treatment and overall survival (OS) between mAA and nAA grouped in SAA and NSAA respectively. In SAA, the reticulocyte count (Ret) of mAA was significantly higher than that of nAA \[23.90(2.99 - 61.00)×10(9)/L vs 13.1(0 - 70.60)×10(9)/L, P = 0.000\] and the proportion of erythroid cells in bone marrow of mAA was also higher \[23.5 (0 - 58) vs 14.5 (0 - 65), P = 0.043\], while they did not differ significantly in NSAA. (3) The proportion of AA with PNH clones or abnormal cytogenetics did not differ significantly in mAA and nAA groups before treatment. The incidences of AA evolved to PNH in mAA and nAA was not statistically significant (7/153 vs 9/376, χ(2) = 1.099, P = 0.294) and so was the incidence of evolution to MDS/AML(3/153 vs 13/376, χ(2) = 0.399, P = 0.528).</p><p><b>CONCLUSION</b>In presented with macrocytic anemia at initial diagnosis of AA, higher proportion of NSAA, elderly age, higher Ret and proportion of erythroid cells are features, but being no statistical difference in the response rate, OS, and proportion of clonal evolution.</p>

Abnormal expression of hMSH2 mRNA and mutation P53 protein in acute lymphoblastic leukemia / 中国实验血液学杂志

In order to investigate the mechanism of acute lymphoblastic leukemic cell malignant proliferation, the expressions of hMSH2 mRNA and mutation P53 (mtP53) protein in bone marrow cells of de novo acute lymphoblastic leukemia (ALL) were determined by in situ hybridization and immunocytochemical methods. The results showed the that percentage of positive cell with hMSH2 mRNA expression was (32.88 +/- 11.46)% in the de novo ALL group and (64.22 +/- 8.51)% in the control group. The percentage of positive cell with mtP53 protein expression was (29.25 +/- 9.45)% in the de novo ALL group, and (12.63 +/- 6.66)% in the control group. There was a significant negative correlation between the positive percentages of hMSH2 mRNA expression and mtP53 protein expression (r = -0.45, P < 0.05). It is concluded that defective MSH2 mRNA expression plays an important role in the pathogenesis of acute lymphoblastic leukemia, mtP53 protein mutation plays an important role in the development of acute lymphoblastic leukemia, the hMSH2 mRNA defect can lead to accumulation of the mutant P53 protein in acute lymphoblastic leukemia, and both jointly promote the pathogenesis of ALL.

Cytotoxic effects of arsenic trioxide in combination with chemotherapeutic drugs on acute non-promyelocytic leukemia cells / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To provide experimental basis for extending the indications of arsenic trioxide (As(2)O(3)) in clinical application.</p><p><b>METHODS</b>MTT assay was used to detect the cytotoxicity of As(2)O(3) in combination with daunorubicin (DNR), cytosine arabinoside (Ara-C), harringtonine (H) and vincristine (VCR) respectively on leukemic cells from 23 newly diagnosed cases with acute non-promyelocytic leukemia (ANPL) and 16 cases of relapsed, refractory ANPL.</p><p><b>RESULTS</b>(1) As(2)O(3) inhibited the growth of leukemic cells from both newly diagnosed or relapsed and refractory ANPL patients, and there was no statistical difference in cytotoxicity of the patients in the two groups [(12.6 +/-7.7 compared with 10.1 +/-6.2)%, P<0.05]. (2) There was no correlation between the cytotoxicities of As(2)O(3) and Ara-C, H or VCR (P<0.05), but a linear correlation between As(2)O(3)and DNR was found (r=0.432, P<0.05).(3) Additivity and synergism of the cytotoxicity was found in most of the ANPL patients when As(2)O(3) was combined with the four chemotherapy drugs and the combination of As(2)O(3) with DNR or VCR enhanced the cytotoxicity significantly (P<0.05).</p><p><b>CONCLUSION</b>The results indicate that As(2)O(3) might be used in treatment of newly diagnosed or relapsed and refractory ANPL patients;and the combination of As(2)O(3) with DNR or VCR may enhance its therapeutic efficacy.</p>

Expression of nuclear factor-kappaB in bone marrow cells from patients with acute leukemia and its relationship with P21, MMP-2 and MMP-9 / 中国实验血液学杂志

To investigate the expression of NF-kappaB in acute leukemia and its relationship with P21, and matrix metalloproteinases (MMP), the expression of NF-kappaB, P21, MMP-2 and MMP-9 in bone marrow cells from patients with acute leukemia (AL) was detected using immunocytochemical technique. The results showed that the expression ratios of NF-kappaB, P21, MMP-2 and MMP-9 in untreated AL group were significantly higher than those in remission and normal control groups (P < 0.05), and no obvious difference was seen between remission and normal control groups. The expression of NF-kappaB was correlated with that of P21, MMP-2 and MMP-9 (r = 0.767, 0.729 and 0.803, respectively, P < 0.05). This study indicated that P21 protein, encoded by oncogene Ras, and NF-kappaB were super-expressed in leukemia cells. In conclusion, after activation by Ras, NF-kappaB combined with the kappaB sequences of MMP-2 and MMP-9 genes, then upregulated their expression. MMP might enhance the degradative function of leukemic cell, thus to make cells easier to cross through the bone marrow barrier and release into blood.

A comparison between immunophenotypes of lymphoid cells from human umbilical cord blood and bone marrow and its significance / 中国实验血液学杂志

To compare the expression of CD antigens on immune cells from umbilical cord blood (UCB) and bone marrow (BM) and analyze its clinical significance, the phenotypes of lymphoid cells and nucleated cells from 38 UCB and 10 BM samples were investigated by flow cytometry with double labeling monoclonal antibodies. The results showed that the immature lymphocytes (CD3(-) CD4(+)) were detected in UCB and higher than those in BM; cytotoxic T lymphocytes (CD3(+) CD16(+) CD56(+)) in UCB were significantly lower than those in BM. NK cells (CD3(-) CD16(+) CD56(+)) in UCB were higher than those in BM. The ratio of CD34(+) cells in nucleated cells of UCB was similar to that of BM, however, both the contents of myeloid (CD34(+) CD13(+) and CD34(+) HLA-DR(+)) and lymphoid (CD34(+) CD19(+)) progenitor cells in UCB were lower than those in BM. It is concluded that the immune cells in UCB possess immaturity, which might lead to mild GVHD after UCB transplantation. It is inferred from the higher ratio of NK cells in UCB, GVL will not decrease after UCB transplantation. The lower contents of myeloid and lymphoid progenitor cells in UCB probably accounted for the slow hematopoiesis and immune reconstitution following UCB transplantation.

Analysis of Clinical and Hematologic Features in 22 Patients with Metastatic Carcinoma of Bone Marrow / 中国实验血液学杂志

The clinical and hematologic features in 22 patients with metastatic carcinoma of bone marrow were observed and analyzed. Morphology of bone marrow cells, bone marrow biopsy and other accessory examinations were performed. The primary or cardinal symptoms of metastatic carcinoma of bone marrow included anemia (17 cases, 77.3%), ostealgia (10 cases, 45.5%), fever (8 cases, 36.4%), hemorrhage (4 cases, 18.2%) and complicated hemolytic anemia (4 cases, 18.2%). The primary carcinomas, diagnosed by pathologic and accessory examinations, include gastric carcinoma (6 cases, 27%), lung cancer (3 cases, 13.6%), ovarian cancer (2 cases, 9%), mammary cancer, prostatic carcinoma, osteocarcinoma and metastatic malignant melanoma (1 case, respectively), and unknown primary lesion (7 cases, 31.8%). The hematologic features were decrease of hemoglobin (17 cases, 77.3%) and blood plate count (16 cases, 72.7%), leukocytosis (11 cases, 50%), immature leukocytes (14 cases, 63.6%) and erythrocytes (9 cases, 40.9%) seen on the peripheral blood smear, and reticulocytosis (4 cases, 18.2%). Masses of metastatic carcinoma cells can be frequently seen at two sides and tail of bone marrow smear. Bone marrow biopsy of 8 cases demonstrated the infiltration of carcinoma cells with nest-like distribution in the bone marrow cavity. Examination of MRI in 6 case showed destruction of bone and corpus vertebra and abnormal signal focus. Bone marrow biopsy could contribute to improve the accuracy of diagnosis and determine the origin of primary carcinoma. MRI plays an important role in diagnosis of metastatic carcinoma in bone marrow.