Imatinib is effective in a 12-month-old boy with chronic myelogenous leukemia: case report and literature review / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize the clinical characteristics of an infant with chronic myelogenous leukemia (CML) and the effects of imatinib on the case.</p><p><b>METHOD</b>The clinical features of an infant with CML, who was treated with imatinib in the Norman Bethune International Peace Hospital at June 2009, were retrospectively analyzed and the reports in literature were reviewed. The 1-year-old boy suffered from recurrent low-degree fever and pallor. He had a moderate anemia, distended abdomen and marked splenomegaly. Bone marrow aspiration revealed CML in chronic phase)CP). The t (9; 22))q34; q11) could be detected and BCR-ABL (p210) was positive. The boy was diagnosed as CML-CP and treated with imatinib 100 mg per day. There were 10 related papers and more than 100 child CML patients were reported as retrieved from CNKI)from its establishment to August 2014) and Wanfang Database)from its establishment to August 2014) when "Child", " Chronic" and "Leukemia" were used as keywords. And there were 30 related papers including 400 cases from PubMed Database (from its establishment to August 2014) and one detailed report of an infant with CML was retrieved when "childhood" and "chronic myeloid leukemia" "imatinib" were used as keywords. The clinical effects of imatinib in infant CML cases were analyzed and summarized based on the literature.</p><p><b>RESULT</b>The boy obtained a complete hematologic response (CHR) at the 6th week of diagnosis, a complete cytogenetic response (CCyR) at the 3rd month and a complete molecular response)CMR) at the 12th month without side effect. This boy grows very well and after a 62-month follow-up, his disease was stable. According to the domestic literature, 5 children CML cases aged 6 -12 years were treated with imatinib without side effects and got complete hematologic response (CHR) after 2-month-therapy. The dose, metabolic characteristics and clinical observation of imatinib can be found in foreign literature and imatinib showed good response with good tolerance in children with CML. Imatinib is regarded as the first line drug for children CML. But it may affect the development of the children.</p><p><b>CONCLUSION</b>The children with CML-CP had a good response to imatinib, but more experience in the treatment of children with CML with iniatinib is needed.</p>

SHP-1 gene in the disease progression of chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the profile of promoter methylation and expression of SHP-1 gene in the progression of chronic myeloid leukemia (CML).</p><p><b>METHODS</b>The expression level of SHP-1 mRNA and protein in bone marrow or peripheral blood mononuclear cells from CML patients were detected by Western blot and SYBR Green-based qRT-PCR. The methylation status of SHP-1 were assessed by methylation-specific polymerase chain reaction (MSP) assay. K562 cells were infected with the lentiviral plasmids pEX-SHP-1-puro-Lv105 (K562-SHP-1) or pEX-EGFP-puro-Lv105 (K562-EGFP). The levels of proteins and phosphorylated proteins were detected by Western blot. qRT-PCR assay was used to test the level of BCR-ABL mRNA.</p><p><b>RESULTS</b>The relative levels of SHP-1 mRNA were sharply decreased in advanced stages CML compared to chronic phase (CP)-CML (0.79±0.37 vs 1.18±0.64, P= 0.009). The level of SHP-1 protein was lower in advanced stages CML compared to CP-CML (0.57±0.02 vs 1.02±0.04, P=0.039). The frequency of SHP-1 gene promoter methylation at selected loci in CP-CML was 23.8% (10/42), and the methylated regions were detected in all advanced CML samples (P<0.01). SHP-1 was stably transfected into K562 cells and selected with puromycin. Overexpression of SHP-1 inhibited the proliferation and induced the apoptosis of K562 cells, meanwhile leaded to G0/G1 phase arrest. After transfection, the level of BCR-ABL mRNA was not affected in K562-SHP-1 cells (1.32±0.34) compared to K562-EGFP cells (1.18±0.20, P=0.644), but overexpression of SHP-1 caused a slight decrease in BCR-ABL protein in K562-SHP-1 cells compared to K562 -EGFP cells (0.78±0.15 vs 1.27±0.24, P=0.040). Overexpression of SHP-1 resulted in a remarkable decrease in MYC protein, phosphorylated forms of JAK2, STAT5, Akt and MAPK. However, the un-phosphorylated forms of these molecules were not significantly affected.</p><p><b>CONCLUSION</b>Decreased expression of SHP-1 caused by aberrant promoter hypermethylation may play a key role in the progression of CML by dysregulation of BCR-ABL, Akt, MAPK, MYC, JAK2 and STAT5 signaling.</p>

The clinical significance and the expression of JAKs and suppressor of cytokine signaling genes in leukemia cells / 中国综合临床

Objective To investigate the expression of suppressor of cytokine signaling genes (SOCSs) and JAKs mRNA in the acute myloid leukemia(AML) patients. Methods The expression of SOCSs and JAKs mRNA as well as TYK2 in AML patients and healthy adults as normal contrals (NC) was measured with RT-PCR. Results The expression of SOCS 1,4,5 and 7 in AML patients was lower than those in normal control and AML with remis-sion (P<0.01),but the expression of SOCS 3 and 6 was higher than those in normal control and remission AML(P<0.01),however there was no significant difference in SOC2 between groups. The expressions of JAK2 ,JAK3 and TYK2 in AML were significantly higher than those in patients with remission and normal control(P<0.05). The ex-pression of JAK1 mRNA in relapsed AML was higher than that in normal control group(P<0.05),but the latter has no statistical significance between beginning treatment and normal group(P>0.05). Conclusion The deletion and degradion of SOCS 1,4,5 and 7 present in AML patients and JAKs expression is significantly increased, suggesting that both of them may co-participate in the pathogenesis of AML.