The prognostic value of cloned genetic mutations detected by second-generation sequencing in RUNX1-RUNX1T1 positive acute myeloid leukemia patients receiving intensive consolidation therapy / 中华血液学杂志

Objective: To investigate the prognostic value of clonal gene mutations detected by second-generation sequencing in patients with positive RUNX1-RUNX1T1 acute myeloid leukemia (AML) who received high-dose chemotherapy or autologous transplantation (intensive consolidation therapy) in the first complete remission (CR(1)) state. Methods: 79 AML patients with positive RUNX1-RUNX1T1 who received intensive consolidation therapy in CR(1) state from July 2011 to August 2017 were analyzed retrospectively. Kaplan-Meier curve and Cox regression model were used to figure out the effect of leukocyte counts at onset and gene mutations for prognosis. Results: C-KIT, FLT3, CEBPA and DNMT3A gene mutations were found in 25 (31.6%) , 6 (7.6%) , 7 (8.9%) and 1 (1.3%) patient among the population. Mutations in C-KIT exon17 and C-KIT exon8 were detected in 19 (24.1%) and 5 (6.3%) cases, respectively, and mutations of FLT3-ITD were confirmed in 5 (6.3%) cases. The higher leukocyte counts presented at onset of leukemia, the shorter overall survival (OS) was seen in these patients (P=0.03) . Patients with C-KIT exon17 mutation had significantly shorter OS (P=0.01) and disease free survival (DFS) (P=0.006) compared with those without gene mutations, and patients with FLT3-ITD gene mutation got the inferior OS (P=0.048) and DFS (P=0.071) . Conclusion: In AML patients with positive RUNX1-RUNX1T1 receiving intensive consolidation therapy, the white blood cell counts at onset of leukemia, C-KIT mutations in exon 17, and FLT3-ITD gene mutations suggest poor prognosis, which would contribute to elaborate risk stratification, personalized treatment and predict prognosis for these patients.

Mutation Spectrum of FANCJ Gene in Adult Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To detect and analyze the mutation status of FANCJ gene in adult AML patients, so as to provide the basis for studying the mechanism of FANCJ driven AML and guiding the preventim and treatment of deseese.@*METHODS@#The cDNAs were extracted and transeripted from bone marrow cells and normal skin cells in 222 newly diagnosed AML patients. The primers were designed for FANCJ gene coding region, the mutations of FANCJ gene coding region in AML patients as well as the mutations of FANCJ gene in mucous membrane epethelia in patients were detected by PCR and sanger seguencing; the evolutionary conservation of FANCJ mutation in different organisms was analyzed by NCBI Blast online bioinformaties software.@*RESULTS@#The sequencing analysis showed that the mutations of FANCJ gene happened in 11 sites of FANCJ gene coding region, which were as followed: exon5:c.G430A:p.A144T, exon6:c.A587G:pN196S, exon9:c.C1255T:p.R419W, exon10:c.G1442A:p.G481D, exon11:c.C1609G:p.L537V, exon16:c.C2360T:p.P787L, exon17:c.C2440T:p.R814C, exon19:c.C2608T:pH870Y, exon19:c.A2686G:p.I896V, exon19:c.C2830G:p.Q944E, exon20:c.G3412A:p.D1138N. Among them, the repeatability existed in mutations of A144T, N196S, R814C, I896V and Q944E. Beside, the mutation sites of A144, R419, G381, L537, P787, H870, Q944 and D1138 were highly conserved in different organisms.@*CONCLUSION@#Among 222 adult AML patients, the mutations of FANCJ gene have been found in 26 patients, moreover, the mutation sites are relatively conserved in different organisms, and possess important fanction. The results of this study provide the basis for exploring the mexhanism of FANCJ gene driven AML and for guiding the prevantion and treatment of AML.

Short-term effects of citrate on markers of bone metabolism in Chinese blood donor volunteers / 中国实验血液学杂志

This study was purposed to investigate the short-term effects of citrate administration on bone metabolism in the healthy blood donor volunteers. A crossover, placebo-controlled trial were conducted on 22 healthy blood donor volunteers. The volunteers received either a standardized infusion of citrate at 1.5 mg/(kg.min) or the equal volume of placebo normal saline, were washout for 2-3 weeks. During washout serial blood samples were collected and analyzed for bone biochemical markers and electrolytes, such as bone formation marker osteocalcin (OC), bone resorption marker carboxyterminal telopeptide of type I collagen (CTX), intact parathyroid hormone ((i)PTH), ionized calcium ((i)Ca(2+)) and phosphorus (P(i)). Serial urine samples were collected and analyzed for Ca(2+), P(i) and creatinine concentration. The results showed that compared with placebo group, infusion of citrate increased serum levels of OC and CTX (p < 0.0001). The greatest increase of OC and CTX levels occurred at the completion of the intervention. The increment of CTX was higher than OC (p = 0.02), and the OC/CTX ratio decreased (p < 0.01). Infusion of citrate also induced profound increase in serum (i)PTH level (p < 0.0001) and urinary calcium excretion (p < 0.0001), and decrease in serum (i)Ca(2+) (p < 0.0001) and P(i) (p < 0.01) levels. The decrease of (i)Ca(2+) level in female was higher than that in male (p = 0.007), but the changes of (i)PTH, OC, and CTX levels showed no differences between female and male. Changes of OC and CTX levels were closely related to each other (r = 0.56, p < 0.0001) and changes of both markers were negatively correlated with the change of serum (i)Ca(2+) concentration during the citrate intervention(r(OC) = -0.44, r(CTX) = -0.44, p < 0.0001). Increased levels of (i)PTH showed positively correlation with OC (r = 0.34, p = 0.02) and borderline correlation with CTX (r = 0.29, p = 0.06) in male. No such relationship was observed in female. All bone markers and electrolyte levels returned to baseline within 24 hours. It is concluded that the citrate load at the dose as a single platelet apheresis results in profound increase of bone turnover, which is characterized by a short-term increase of bone resorption and excretion of calcium. The possible effect of citrate on bone mass of long-term frequent platelet apheresis donor is worth concerning.