Karyotypic analysis and prognosis for 41 patients with chronic myelomonocytic leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze cytogenetic features of chronic myelomonocytic leukemia (CMML) patients and explore the relationship between cytogenetic characteristics and prognosis.</p><p><b>METHODS</b>Clinical and laboratory data of 41 CMML patients were analyzed.</p><p><b>RESULTS</b>The majority of CMML patients were middle-aged males. According to WHO classification, 17 (41.5%) patients were diagnosed as CMML-Ⅰ and 24 (58.5%) were diagnosed as CMML-Ⅱ. 14 (34%) of CMML patients harbored abnormal karyotypes and +8 was the most common. CMML-Ⅰpatients with abnormal karyotypes were older than those with normal karyotypes. CMML-Ⅱ patients with normal karyotypes had higher lymphocyte counts than those with abnormal karyotypes. Of 29 patients who had follow-up data, 26 died, with the median survival time being 4 (1-13) months. The median survival of patients with normal and abnormal karyotypes were 4.5 and 3.8 months, respectively (P=0.408). The median survival of CMML-Ⅰ patients with abnormal karyotypes was shorter than those with normal karyotypes (3 and 17 months, P=0.015), but no significant difference was found between the median survival of the two groups of CMML-Ⅱ patients (2.9 and 5.8 months, P=0.629).</p><p><b>CONCLUSION</b>+8 has been the most common abnormal karyotype in CMML patients. The abnormal karyotype can be regarded as an indicator of poor prognosis for CMML-Ⅰ patients. Regardless of their karyotypes, CMML-Ⅱ patients have even poorer prognosis.</p>

Expression of BCL2L12 gene in de novo acute myeloid leukemia and its clinical implications / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the expression of BCL2L12 gene and its clinical significance for de novo acute myeloid leukemia (AML).</p><p><b>METHODS</b>Real-time quantitative PCR (RQ-PCR) was employed to measure the expression of BCL2L12 gene in 134 patients with de novo AML. The results were correlated with clinical features of patients.</p><p><b>RESULTS</b>BCL2L12 gene transcript was determined for 134 AML patients and 49 healthy controls, with the median levels measured 0.1029 (0.0119-26.4090) and 0.2677 (0.0173-1.2858), respectively. There was a significant difference in the strength of BCL2L12 gene expression between patients and normal controls (P < 0.01). Those with lower BCL2L12 expression levels had a higher FLT3-ITD mutation rate compared with those with higher levels (27% vs. 5%, P = 0.036). Relapsed or refractory AML patients had lower expression compared with newly diagnosed patients (0.0873 vs. 0.1359, P = 0.014). There was no difference in overall survival (OS) between patients with higher and lower expression levels. However, for AML patients with a normal karyotype, the OS for those with lower expression was significant shorter (P = 0.037).</p><p><b>CONCLUSION</b>De novo AML patients have a lower level of BCL2L12 gene expression. AML patients with lower BCL2L12 expression have a higher FLT3-ITD mutation rate, and most of them are relapse or refractory patients. In addition, among patients with a normal karyotype, those with a lower BCL2L12 expression have a shorter OS. Therefore, expression of the BCL2L12 gene may be used as a prognostic marker for AML patients with a normal karyotype.</p>

Expression level of CDX2 gene in acute myeloid leukemia and its clinical significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore the expression and clinical significance of Caudal-type homeobox transcription factor 2 (CDX2) gene in acute myeloid leukemia (AML) patients.</p><p><b>METHOD</b>Real time quantitative PCR (RQ-PCR) was used to test the expression level of CDX2 gene in 108 de novo AML patients and the clinical features of these patients were analyzed.</p><p><b>RESULTS</b>CDX2 gene transcript levels were detectable in bone marrow mononuclear cells from 108 AML patients and 7 healthy donors, the median expression level were 1179.44 (range 14.15 - 867 961.10) and 105.30 (range 22.30 - 453.11). There was a statistically significant difference in expression level of CDX2 gene between the AML patients and normal donor (P < 0.01). All 14 patients with FLT3-ITD(+) were in CDX2 gene higher expression group (P = 0.018), including 10 patients with normal karyotype. In the 83 treated AML patients (P = 0.046) and 57 higher WBC count (≥ 10×10(9)/L, P = 0.048) patients, the higher expression level of CDX2 gene was associated with lower complete remission (CR) rates.</p><p><b>CONCLUSIONS</b>Higher expression level of CDX2 gene was seen mostly in AML patients with FLT3-ITD mutation and with lower CR rates. CDX2 gene might be a prognostic molecular marker in AML patients with normal karyotype.</p>

Establishment of a rapid and easy method for simultaneous detection of FLT3-ITD and NPM1 gene mutations in acute myeloid leukemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish a stable, rapid multiplex PCR assay combined with PAGE gel electrophoresis for simultaneously detecting FLT3-ITD and NPM1 mutations in acute myeloid leukemia (AML).</p><p><b>METHODS</b>Capillary electrophoresis (CE) and PAGE gel electrophoresis were simultaneously used to analyze FLT3-ITD and NPM1 mutations in 117 de novo AML patients with normal cytogenetic findings.</p><p><b>RESULTS</b>For certain mutations, the length of mutated double-stranded DNA is longer than wild-type DNA. Since FLT3-mut (420 bp) is longer than FLT3-wt (327-332 bp), and NPM1-mut (172 bp) is longer than NPM1-wt (168 bp), heteroduplex will move more slowly during PAGE gel electrophoresis than homoduplex. Therefore the mutations may be detected. A total of 117 CN-AML patients were analyzed with CE and PAGE gel electrophoresis, and the results were identical, which included 18 (15.4%) patients with FLT3-ITD+/NPM1-, 19 (16.2%) patients with FLT3-ITD+/NPM1+, 25 (21.4%) patients with FLT3-ITD-/NPM1+, and 55 (47.0%) patients with FLT3-ITD-/NPM1-.</p><p><b>CONCLUSION</b>Both types of electrophoresis assays may provide a rapid and handy assay for simultaneous detection of FLT3-ITD and NPM1 mutations. CE is relatively sensitive, stable; while PAGE electrophoresis is relatively simple, cheap, and reliable, which may be suitable for primary hospitals and preliminary screening.</p>