Genetic characteristics and survival analysis of 27 cases of juvenile myelomonocytic leukemia / 中华儿科杂志

Objective: To investigate the genetic and genomic profiling of juvenile myelomonocytic leukemia (JMML) and factors affecting its survival rate. Methods: Clinical characteristics, cytogenetics, molecular biology results and survival status of children with 27 JMML cases admitted to the Hematology Department of Children's Hospital, Capital Institute of Pediatrics from December 2012 to December 2021 were analyzed retrospectively, and the outcomes of the children were followed up. Kaplan-Meier method was used for survival analysis. Univariate analysis was used for analyzing factors affecting the overall survival (OS) rates of patients who received hematopoietic stem cell transplantation (HSCT). Log-Rank test was used for comparison of survival curves. Results: Among 27 JMML cases, there were 11 males and 16 females. The age of disease onset was 28 (11,52) months. There are 20 cases of normal karyotype, 4 cases of monosomy 7, 1 case of trisomy 8,1 case of 11q23 rearrangement and 1 case of complex karyotype. A total of 39 somatic mutations were detected.Those involved in RAS signal pathway were the highest (64%(25/39)), among which PTPN11 mutation was the most frequent (44% (11/25)). A total of 17 cases (63%) received HSCT, 8 cases (30%) did not receive HSCT, and 2 cases (7%) lost follow-up. For children receiving transplantation, the follow-up time after transplantation was 47 (11,57) months. The 1-year OS rate of high-risk transplantation group (17 cases) and high-risk non transplantation group (6 cases) was (88±8)% and (50±20)% respectively, with a statistically significant difference (χ2=5.01, P=0.025). The 5-year OS rate of the high-risk transplantation group was (75±11)%. The survival time of those who relapsed or progressed to acute myeloid leukemia after transplantation was significantly shorter than that of those who did not relapse (χ2=6.80, P=0.009). The OS rate of patients with or without PTPN11 mutation was (81±12) % and (67±19)% respectively (χ2=0.85, P=0.356). Conclusions: The main pathogenesis involved in JMML is gene mutation related to RAS signaling pathway, and the most common driver gene of mutation is PTPN11. Allogeneic HSCT can significantly improve the survival rate of high-risk JMML patients. The recurrence or progression after transplantation was related to poor prognosis.

Nilotinib treatment for patients with imatinib-resistant or intolerant chronic myeloid leukemia / 中国实验血液学杂志

This study was purposed to evaluate the efficacy and safety of nilotinib for treating patients with imatinib-resistant or intolerant chronic myeloid leukemia (CML). A total of 23 patients with imatinib-resistant or intolerant CML were enrolled in this study. These patients received nilotinib orally 600-800 mg every day, their curative efficacy, tolerance and overal survival were evaluated. The results showed that all the patients treated with nilotinib obtained complete hematologic remission (CHR), out of them 82.6% patients achieved complete cytogenetic remission (CCyR) and 56.5% patients achieved complete molecular remission (CMR), their adverse events mostly were mild to moderate, generally were transient and easily cured; the median treatment time with nilotinib was 13.5 (1-44) months, and the median follow-up time was 40 (12-102) months. It is concluded that nilotinib has been confirmed to be effective for patients with imatinib-resistant or intolerant CML, and may be selected as a second generation of tyrosine kinase inhibitor (TKI).

Suppression of survivin gene in leukemia cells by small interfering RNA / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the impact of specific siRNA on survivin gene in transfected leukemia cells.</p><p><b>METHOD</b>The small interfering RNA (siRNA) targeted survivin mRNA was synthesized in vitro and was transfected into K562 cell by Hiperfect into human leukemia cell line K562, which has high survivin expression level. The level of survivin mRNA expression was determined by quantitative reverse transcription polymerase chain reaction (RT-PCR) with SYBR GREEN I. The apoptosis index of cytotrophoblasts were determined and analyzed by FCM (Annexin V-FITC/PI staining methods). The cell proliferation was examined by MTT at 48 h and 72 h after transfection.</p><p><b>RESULT</b>The level of mRNA expression was significantly inhibited by the siRNA 48 h and 72 h after transfection, the suppression rate of survivin mRNA separately reached 85.21%, 94.35% mensurated by quantitative RT-PCR with SYBR GREEN I, cell proliferation was inhibited significantly by 45.02% and 50.88%, respectively, the apoptotic rate detected by Annexin V-FITC assay reached 12.28%and 21.55%, respectively.</p><p><b>CONCLUSION</b>The chemosynthesized siRNA targeting survivin could significantly down-regulate survivin mRNA. Survivin siRNA was able to inhibit the proliferation of leukemia cell line K562. Survivin may become a new target for leukemia gene therapy.</p>