Loss of miR-146b-5p promotes T cell acute lymphoblastic leukemia migration and invasion via the IL-17A pathway.

Metastatic disease remains the primary cause of death for individuals with T cell acute lymphoblastic leukemia (T-ALL). microRNAs (miRNAs) play important roles in the pathogenesis of T-ALL by inhibiting gene expression at posttranscriptional levels. The goal of the current project is to identify any significant miRNAs in T-ALL metastasis. We observed miR-146b-5p to be downregulated in T-ALL patients and cell lines, and bioinformatics analysis implicated miR-146b-5p in the hematopoietic system. miR-146b-5p inhibited the migration and invasion in T-ALL cells. Interleukin-17A (IL-17A) was predicted to be a target of miR-146b-5p; this was confirmed by luciferase assays. Interestingly, T-ALL patients and cell lines secreted IL-17A and expressed the IL-17A receptor (IL-17RA). IL-17A/IL-17RA interactions promoted strong T-ALL cell migration and invasion responses. Gene set enrichment analysis (GSEA) and quantitative polymerase chain reaction (qPCR) analysis indicated that matrix metallopeptidase-9 (MMP9), was a potential downstream effector of IL-17A activation, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling was also implicated in this process. Moreover, IL-17A activation promoted T-ALL cell metastasis to the liver in IL17A -/- mouse models. These results indicate that reduced miR-146b-5p expression in T-ALL may lead to the upregulation of IL-17A, which then promotes T-ALL cell migration and invasion by upregulating MMP9 via NF-κB signaling.

LINC00853 restrains T cell acute lymphoblastic leukemia invasion and infiltration by regulating CCR9/CCL25.

BACKGROUND: Leukemia is a group of hematopoietic malignancies characterized by the accumulation and infiltration of abnormal hematopoietic stem cells or early progenitor cells. T cell acute lymphoblastic leukemia (T-ALL) is a hematologic malignancy occurring in 15 % of pediatric and 25 % of adult ALL cases. Infiltration and metastasis of leukemic cells to specific organs are consequences of disease relapse and dismal prognosis. Long non-coding RNAs (lncRNAs) have been identified to function in the migration, invasion and infiltration of tumors by regulating gene expression. Our previous studies showed that CC chemokine receptor 9 (CCR9), which specifically bind to CC chemokine ligand 25 (CCL25), promotes T-ALL infiltration. METHODS: Bioinformatic methods were used to screen LINC00853 in gene expression omnibus (GEO) datasets. RT-qPCR, western bolt and flow cytometry were applied to detect the expression of LINC00853 and CCR9. Transwell and martrigel-transwell were employed to assess the cells migration and invasion abilities. Fluorescence microscope was applied to observed the green fluorescence protein positive (GFP+) cells. Lentivirus and adenovirus were packed to construct nc-blank, sh-LINC00853-blank and sh-LINC00853-rescue jurkat cell lines. RESULTS: In this study, we found out the negative correlation of LINC00853 and CCR9 expression. LINC00853 was downregulated while CCR9 was upregulated in GEO datasets, T-ALL cell lines and clinical samples. Moreover, LINC00853 suppressed jurkat cells migration and invasion in vitro and restrained infiltration in liver, spleen, kidney, lung, brain, ovary of nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. CONCLUSIONS: These findings indicate that LINC00853 restrains T-ALL cell invasion and infiltration by regulating CCR9/CCL25.

[HAA regimen as induction chemotherapy for newly diagnosed acute myelogenous leukemia].

OBJECTIVE: To analyse the outcome of newly diagnosed adult acute myeloid leukemia (AML) patients treated with HAA (homoharringtonine, cytarabine and aclarubicin) regimen and explore the efficacy and safety of this regimen. METHODS: Eighty patients were treated with HAA regimen. The complete remission (CR) rate was observed. Kaplan-Meier method was used to estimate relapse free survival (RFS) rate and the differences were compared with 2-sided log-rank test. RESULTS: Of the 80 patients, 65 (81%) attained CR and the CR rate after the first course of induction was 75%. For the CR patients, the median follow-up was 26 (2 -69) months, and the estimated 3-year overall survival (OS) rate was 51% and the estimated 3-year RFS was 53%. For the AML-M5 and AML-M /M2 patients the CR rate was 74% and 87% and 3 year RFS of CR patients was 75% and 37%, respectively. The CR rate of 100%, 83% and 20% was achieved in patients with favorable, intermediate and unfavorable cytogenetics, respectively. The 3 year OS for favorable and intermediate group was 76% and 50% respectively. The median survival time of unfavorable group was only 6 months. CONCLUSION: HAA regimen is a safe, efficacious, and well-tolerable induction therapy for newly diagnosed AML.

[Cytogenetic and molecular analysis of 1193 cases with chronic myeloid leukemia].

OBJECTIVE: To evaluate the cytogenetic and molecular genetic features of chronic myeloid leukemia (CML) in Chinese. METHODS: A total of 1193 CML patients were retrospectively studied. Chromosome preparation of bone marrow cells was made using direct and short-term culture. Karyotype and bcr-abl fusion genes were analyzed by R-banding, RT-PCR, respectively. RESULTS: In the 1193 cases, 98.07% was Ph chromosome positive (Ph+) and 1.93% negative (Ph-). In the Ph+ patients, 95.64% was classical Ph and 4.36% variant rearrangements. Additional genetic changes were demonstrated in 11.88% of classical Ph cases. Cytogenetic clonal evolution was found in 7.94% of patients in chronic phase (CP), 27.78% in accelerated phase (AP), and 49. 04% in blast crisis (BC). Among the classical Ph cases, +Ph, +8, -21 were found in 14.62%, 10.77% and 7.69% of them respectively. In patients in BC and AP, the most common additional chromosome changes were + Ph (28.57%), +8 (16.67%) and +19 (7.14%), while in CP, -21 (10.26%), +Ph (8.97%), and +8 (8.97%). The combination of +Ph and +8 (3.60%) was the most frequent of combination pattern. 524 cases were investigated for bcr-abl fusion gene, and 54.01% was b3a2 (+) and 27.67% b2a2 (+). CONCLUSION: In Chinese CML patients seem to have their unique features in terms of cytogenetic clonal evaluation.

[Special morphological changes of pathologic cells in two cases of Waldenström's macroglobulinemia].

Waldenström's macroglobulinemia (WM) is one of malignant hematological disease on account of abnormal proliferation of B lymphocyte clone and the pathologic cells of WM possess ability to secrete monoclonal immunoglobulin M. In this study, the diagnosis and morphological characteristics of 2 patients with WM were analyzed. The results showed that a special kind of "foam cells" were found by cytochemical staining examinations in both cases, which displayed characteristics of lymphocytes, but neither monocyte-macrophage nor fatty cells. The periodic acid-Shiff's reaction (PAS) demonstrated strong positive, especially on the inclusion bodies in pathologic cell plasma while the acid phosphatase, and alpha-butanoic acetate esterase stainings, resulted both in negative. In conclusion, the cells found in the two cases reported may be described as gemmy ring-like lymphocyte in morphology, a special subtype of ring-like lymphocyte.