Deletions in IKZF1 are found in ~15% of children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). There is strong evidence for the poor prognosis of IKZF1 deletions affecting exons 4-7 and exons 1-8, but evidence for the remaining 33% of cases harboring other variants of IKZF1 deletions is lacking. In an international multicenter study we analyzed the prognostic value of these rare variants in a case-control design. Each IKZF1-deleted case was matched to three IKZF1 wild-type controls based on cytogenetic subtype, treatment protocol, risk stratification arm, white blood cell count and age. Hazard ratios for the prognostic impact of rare IKZF1 deletions on event-free survival were calculated by matched pair Cox regression. Matched pair analysis for all 134 cases with rare IKZF1 deletions together revealed a poor prognosis (P<0.001) that was evident in each risk stratification arm. Rare variant types with the most unfavorable event-free survival were DEL 2-7 (P=0.03), DEL 2-8 (P=0.002) and DEL-Other (P<0.001). The prognosis of each type of rare variant was equal or worse compared with the well-known major DEL 4-7 and DEL 1-8 IKZF1 deletion variants. We therefore conclude that all variants of rare IKZF1 deletions are associated with an unfavorable prognosis in pediatric BCP-ALL.

• MeSH
• delece genu * MeSH
• dítě MeSH
• dospělí MeSH
• fúzní onkogenní proteiny analýza   MeSH
• kojenec MeSH
• lidé MeSH
• mezinárodní spolupráce MeSH
• mladiství MeSH
• pre-B-buněčná leukemie genetika   mortalita   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• protein PEBP2A2 analýza   MeSH
• transkripční faktor Ikaros genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Our objective was to determine the value of frequent minimal residual disease (MRD) monitoring in acute myeloid leukemia (AML) as a robust marker of impending relapse, and whether treatment benefits patients during the MRD-positive phase of their disease. MATERIALS AND METHODS: Frequent MRD monitoring was performed in all AML treatment phases using real-time quantitative polymerase chain reaction for fusion transcripts (CBFB/MYH11; RUNX1/RUNX1T1 fusion transcripts of MLL gene) and for the Wilms' tumor (WT1) gene. A total of 2,664 samples, taken from 79 AML patients and 6 healthy volunteers, were examined. Presence of fusion gene was detected in 25 of 79 examined patients. RESULTS: Vast correlation was discovered for fusion transcripts as well as for the WT1 gene between levels in bone marrow (BM), peripheral blood, CD34(+) BM cells, and CD34(-) BM cells. WT1 expression, however, was usually positive for cases showing fusion transcripts negativity and in healthy volunteers. Moreover, no universal value of the WT1 expression could unequivocally discriminate between remission and relapse. Therefore, detection of molecular relapses relied on fusion transcripts only and was characterized by strong expression in CD34(+) cells. Considering relapsed patients, duration from molecular to hematological relapse was 8 to 79 days (median: 25.5 days). Twelve patients were treated (chemotherapy, gemtuzumab ozogamicin, or immunomodulation after allogeneic transplantation) for 21 molecular relapses and 14 responses to treatment were observed. CONCLUSIONS: Frequent quantitative monitoring of fusion transcripts is useful for reliably predicting hematological relapse in AML patients. Treatment for molecular relapse of AML can be successful.

• MeSH
• akutní myeloidní leukemie diagnóza   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nádorové biomarkery analýza   MeSH
• nádorové proteiny analýza   MeSH
• protein CBFB analýza   MeSH
• protein PEBP2A2 analýza   MeSH
• proteiny WT1 analýza   MeSH
• protoonkogenní protein MLL analýza   MeSH
• recidiva MeSH
• reziduální nádor diagnóza   terapie   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• translokace genetická MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH