| Background:Pedeiatric B-cell Acute Lymphoblastic Leukmia(BPC-ALL)has become the model of curable hematologic tumor.On the contrast,the overall prognosis of adult ALL is still poor,and the long-term survival rate is just about 50%.One of the most significant reasons leading to the drug resistantance or recurrence in adult ALL is the evolution of leukemia cell cloning.It’s reported that IKZF1 gene deletion plays an important role in the pathogenesy of ALL.The Ikaros protein,encoded by IKZF1,is a member of the zinc finger DNA binding protein family which is a major,non-redundant regulator of B cell development and differentiation,and mature as well.IKZF1 gene mutation is the typical molecular genetic characteristic of Philadelphia chromosome positive acute lymphoblastic leukemia(Ph+ ALL)and Ph-like ALL,and it is also an independent prognostic factor for BCP-ALL.However,the report about expression and significance of IKZF1 gene in BCP-ALL before or after treatment,or even in the recurrence of BCP-ALL is still rare.Objective:(1)To detect and analyze the proportion of total deletion and subtype deletion of IKZF1 gene in first-diagnosed and relapsed BCP-ALL cases.(2)To analyze the prognostic significance of IKZF1 gene deletion in first-diagnosed and relapsed BCP-ALL cases respectively.(3)To track the change of IKZF1 gene deletion of paired samples,and to explore its significance in the evolution of recurrence of BCP-ALL cases.Methods:The DNA specimens of a total of 104 cases of first-diagnosed BCP-ALL in Nanfang Hospital from September 2011 to August 2017 were collected,and the IKZF1 gene exon deletion was detected by GAP-PCR.Then we retrospectively analyzed the relationship between IKZF1 gene mutation and prognosis.At last we analyzed the changes of IKZF1 genetic deletion with 45 matched-samples from relapsing patients.Results:(1)In the first-diagnosed BCP-ALL cases,the deletion of IKZF1 gene exons were detected in 42 patients.It’s much more normal in Ph+ALL than in the Ph-BCP-ALL(57.6%vs 17.8%,p<0.001).In relapsed cases,the IKZF1 gene deletion was associated with a detection rate of 51.1%(23/45),and the main subtypes includes △4-7(n=13),△2-7(n=3).In relapsed Ph+ALL cases,the positive rate of the IKZF1 gene deletion was 65.2%,which was significantly higher than that of Ph-BCP-ALL(65.2%vs 34.8,p=0.004),and the main subtypes is △4-7(n=13).(2)The first-diagnosed,BCP-ALL patients were divided into the gene missing subgroup and the non-missing subgroup according to the initial IKZF1 detection state.The results show that there is no significant difference between the patients with the IKZF1 gene deletion and those without IKZF1 gene deletion in progression free survival rate and 1-year overall survival rate.The relapsed BCP-ALL patients were divided into the gene missing subgroup and the non-missing subgroup according to the IKZFl detection state in relapsed period.The results show that the Ph+ ALL patients with IKZF1 gene deletion has a significantly lower 1-year overall survival rate(43.7%)than those without IKZF1 gene deletion(88.9%)(p =0.047).(3)To compare the subtypes of IKZF1 gene deletion of the periods between first-diagnosed and relapsed in 45 relapsed cases of BCP-ALL,we found several changes of IKZF1 gene mutation in 11 groups(24.4%).In 20 Ph+ ALL cases,IKZF1 gene mutation clones disappeared in 5 groups during relapsed period.In 25 Ph-BCP-ALL,IKZF1 gene mutation clones disappeared during the relapsed period in 3 cases of the groups;the new clones were found in the relapsed stage in the other 3 cases.Discussion:The deletion of IKZF1 gene has not only a high detection rate in BCP-ALL,but a bad prognostic significance for Ph+/Ph-ALL patients or first-diagnosed/relapsed patients.The dynamic changes of IKZF1 gene deletion is one of the important molecular genetic characteristics of clonal evolution of relapsed BCP-ALL.So the mechanism of IKZF1 gene deletion in clonal evolution and how to target IKZF1 gene deletion is worth further studying. |
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