Carnosic Acid-combined Arsenic Trioxide Antileukaemia Cells in the Establishment of NB4/SCID Mouse Model.

Despite great improvement in the treatment outcome of APL, treatment failure still sometimes occurs due to the toxicity of arsenic trioxide (ATO). Damage to the heart and liver often occurs even when the dose is lower than the therapeutic dose. Based on the results of cell experiments in vitro in this study, we investigated the synergistic activity of carnosic acid (CA) combined with ATO in the SCID mouse model of human promyelocytic leukaemia in vivo. A NB4/SCID mouse model was established in this study. The NB4/SCID mice were randomly divided into three treatment groups (CA alone, ATO alone and CA combined with ATO) and a control group based on factorial design. The evaluation indicators of the curative effect of the drugs included expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins by immunohistochemistry, flow cytometry and Western blot analysis. The survival time was compared between the four groups. The results indicated that verification of the NB4/SCID mouse model was confirmed by histopathological examination. Compared with mice treated by CA or ATO alone, the mice in the combination of CA and ATO group had a higher rate of apoptosis, which was linked with expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins. Also, the mice with the longest survival time were those treated with the combination of CA and ATO. In conclusion, the results of the present study indicated that CA and ATO in combination have strong synergistic antileukaemic effects on cell activity.

A case of simultaneous occurrence of acute myeloid leukemia and multiple myeloma.

BACKGROUND: Although the occurrence of acute myeloid leukemia (AML) after chemotherapy for multiple myeloma (MM) is common in clinical settings, the simultaneous occurrence of these malignancies in patients without previous exposure to chemotherapy is a rare event. Etiology, disease management, and clinical treatment remain unclear for this particular occurrence. To the best of our knowledge, this study is the first to report a case of simultaneous presentation of AML and MM after exposure to ultraviolet irradiation. CASE PRESENTATION: We reported the case of a 73-year-old man (Han Chinese ethnicity) without previous medical history of AML and MM. The morphology and immunology of bone marrow cells confirmed the co-existence of AML and MM. Fluorescent in situ hybridization analysis of immunomagnetically separated abnormal plasma cells showed abnormal expression of the amplified RB-1, TP53, and CDKN2C (1p32). Cytogenetic analysis demonstrated Y chromosome deletion. After the patient was administered with bortezomib combined with cytarabine + aclarubicin + granulocyte colony-stimulating factor (CAG regimen), and evident curative effects were observed. The patient achieved and maintained complete remission for more than 6 months. Prior to the disease occurrence, the patient had received ultraviolet irradiation for 1 year and was detected with aberrant gene expression of RB-1, TP53, and CDKN2C (1p32). Nevertheless, the correlation of this phenomenon with the etiology of concurrent AML with MM remains unclear. CONCLUSION: This study discussed the case of a patient diagnosed with AML concurrent with MM, who has no previous exposure to chemotherapy. This patient was successfully treated by bortezomib combined with CAG regimen. This study provides a basis for clinical treatment guidance for this specific group of patients and for confirmation of the disease etiology.

Clinical study on prospective efficacy of all-trans Acid, realgar-indigo naturalis formula combined with chemotherapy as maintenance treatment of acute promyelocytic leukemia.

Objectives. To test the efficiency and safety of sequential application of retinoic acid (ATRA), Realgar-Indigo naturalis formula (RIF) and chemotherapy (CT) were used as the maintenance treatment in patients with acute promyelocytic leukemia (APL). Methods. This was a retrospective study of 98 patients with newly diagnosed APL who accepted two different maintenance treatments. After remission induction and consolidation chemotherapy according to their Sanz scores, patients received two different kinds of maintenance scheme. The first regimen was using ATRA, RIF, and standard dose of CT sequentially (ATRA/RIF/CT regimen), while the second one was using ATRA and low dose of chemotherapy with methotrexate (MTX) plus 6-mercaptopurine (6-MP) alternately (ATRA/CTlow regimen). The OS, DFS, relapse rate, minimal residual disease, and adverse reactions in two groups were monitored and evaluated. Results. ATRA/RIF/CT regimen could effectively reduce the chance of relapse in different risk stratification of patients, but there was no significant difference in 5-year DFS rate and OS rate between the two groups. Besides, the patients in the experimental group suffered less severe adverse reactions than those in the control group. Conclusions. The repeated sequential therapeutic regimen to APL with ATRA, RIF, and chemotherapy is worth popularizing for its high effectiveness and low toxicity.

Relationship of TGF-β and IL-4R gene polymorphisms with risk of classical Hodgkin lymphoma / 中华血液学杂志

<p><b>OBJECTIVE</b>This study was aimed to analyze the relationship between single nucleotide polymorphisms of transforming growth factor-β1 G-800A and C-509T, interleukin-4 receptor V75I and susceptibility of CHL in adults.</p><p><b>METHODS</b>Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to analyze the expressed alleles of the selected SNP loca. The relationship between genomic polymorphisms of TGF-β1 and IL-4R and susceptibility of CHL were coupled with clinical data.</p><p><b>RESULTS</b>TGF-β1G-800A and TGF-β1C-509T had obvious linkage equilibrium (D' = 0.879, r(2) = 0.83, P = 0.020). GT haplotype distribution frequencies in mixed cellularity Hodgkin lymphoma cases and control group were of 53.1% and 34.2%, respectively, with statistically significant (OR = 2.35, P = 0.000); distribution frequencies of mutant gene T/T in disease and control groups were of 38.8% and 15.3%, respectively, also with statistically significant (OR = 3.654, P = 0.000); frequencies of nodular sclerosis CHL patients with IL-4R V75I mutant gene A/A in disease and control groups were of 19.2% and 41.75%, respectively, also with statistically significant (OR = 3.156, P = 0.000).</p><p><b>CONCLUSION</b>Single nucleotide polymorphisms of TGF-β1 G-800A, C-509T and IL-4R V75I has a significant correlation with Chinese susceptibility to classical Hodgkin lymphoma.</p>

Monitoring of plasma concentration of imatinib mesylate in patients with chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyze the clinical efficacy of imatinib mesylate (IM) for Ph-positive or BCR-ABL positive chronic myeloid leukemia (CML) to couple the trough plasma concentrations (C mins) of IM with clinical responses and adverse events (AEs).</p><p><b>METHODS</b>One hundred and one CML patients received IM therapy, and Cmins of IM were determined in 30 patients.</p><p><b>RESULTS</b>(1) Cumulative complete hematological response (CHR), major cytogenetic response (MCyR), complete cytogenetic response (CCyR) and negative BCR/ABL fusion gene rates were 96.6%, 86.5%, 77.5% and 47.2%, respectively, in CML-CP patients. In accelerated and blastic phases (AP and BC) patients, CHR, MCyR, CCyR and negative BCR-ABL fusion gene rates were 58.3%, 25.0%, 25.0%, 8.3%, respectively. (2) Mean Cmins of IM was significantly higher in the CCyR at 1 year [(1472 +/- 482) microg/L] group than in the non-CCyR at 1 years group [(1067 +/- 373) microg/L] (P < 0.05), and higher in the MMR at 1 year group than in the non-MMR at 1 years group [(1624 +/- 468) microg/L vs (1137 +/- 404) microg/L, P < 0.05].</p><p><b>CONCLUSION</b>IM significantly improves cytogenetic and molecular response, event-free survival, and overall survival for patients with Ph-positive CML. The Cmins of IM exerts a significant impact on clinical response (CCyR and MMR at 1 year).</p>