Rationale:Philadelphia chromosome positive acute myeloid leukemia (Ph+ AML) is a rare subtype of AML that is now included as a provisional entity in the 2016 revised WHO classification of myeloid malignancies. However, a clear distinction between de novo Ph+ AML and chronic myeloid leukemia blast crisis is challenging. It is still a matter of debate whether Ph+ AML patients should be treated with chemotherapy or tyrosine kinase inhibitors as first-line therapy.Patient concerns:We reported here a case of a 46-year-old man who was diagnosed as Ph+ AML. This diagnosis was confirmed by bone marrow pathology and karyotype analysis of 46, XY, t (9; 22). Further examination, molecular genetic analysis showed BCR/ABL1 (p190) without ABL1 kinase domain mutations, and direct evidence demonstrated in AML by flow cytometry.Diagnosis:The diagnosis of Ph+ AML was made on May 2016 according to morphology, immunology, cytogenetic, and molecular criteria, and multiple organ failure was also diagnosed.Interventions:The patient was treated with dasatinib as the only medication after experiencing multiple organ failure. Then, he received 2 cycles of chemotherapy with IA (idarubicin 8 mg/m2, day 1–3; cytarabine 100 mg/m2, day 1–7) in August, 2016.Outcomes:The patient finally achieved a complete molecular remission.Lessons:This case study suggests that dasatinib can be a safe and effective treatment for Ph+ AML patients with poor physical condition.

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DOX/GA–CdTe–CD22 can precisely target lymphoma and deliver DOX and GA to lymphoma cells to improve their therapeutic effects.

Background:Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 (Wog-MNPs-Fe3O4) as an antileukemia agent.Methods:After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe3O4 on K562/A02 cells were determined by methyl thiazolyl tetrazolium (MTT) assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4 were determined by flow cytometer (FCM) assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR).Results:With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe3O4 was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe3O4 had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe3O4 group (28.64–68.36%) were significantly lower than those of the wogonin group (35.53–97.28%) in a dose-dependent manner in 48 h (P < 0.001). The apoptotic rate of K562/A02 cells was significantly improved in 50 μmol/L Wog-MNPs-Fe3O4 group (34.28%) compared with that in 50 μmol/L wogonin group (23.46%; P < 0.001). Compared with those of the 25 and 50 μmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 μmol/L Wog-MNPs-Fe3O4 groups (all P < 0.001). The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4 group compared with those of the wogonin group (all P < 0.001).Conclusions:This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.

BackgroundTKIs are the first-line treatment for patients with Ph-positive (Ph+) leukemia. However, drug resistance is frequently observed, mainly due to mutations within the breakpoint cluster region-Abelson leukemia virus (BCR-ABL) kinase domain. The T315I substitution confers complete resistance to TKIs. The aim of this study was to analyze the clinical characteristics of 17 patients with T315I mutation after TKI treatment and provide a basis for prognosis.Patients and methodsThe clinical data of 17 TKI-resistant Ph+ leukemia patients who were found to have a ABL kinase domain mutation from September 2008 to January 2017 were collected. Karyotypes and BCR-ABL fusion gene were analyzed by R-banding and fluorescence in situ hybridization, respectively. Total RNA was extracted by TRIzol reagent, and the ABL kinase domain mutation was detected by direct sequencing.ResultsA total of 17 patients reached effective remission including major molecular response and complete cytogenetic response. However, all the patients subsequently developed a T315I mutation after treatment with TKIs. The rate of the BCR-ABL fusion gene in most of the patients who developed the T315I mutation was significantly higher than that before the mutation. At initial diagnosis, patients average platelet count was 149.7×109/L, whereas the average platelet count was only 53.88×109/L after the T315I mutation (P<0.01). The results also showed that the survival time of patients with a high proportion of blast cells or a high number of white blood cells was obviously shortened.ConclusionPatients platelet count decreased when detected with the T315I mutation compared with the initial diagnosis. Combined use of different TKIs and complex chromosomal karyotypes may promote the development of the T315I mutation. When the ratio of blast cells was >50% and the number of white blood cells was >20×109/L, poor survival prognosis was observed.