BACKGROUND: Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studies typically did not explore the prognostic impact of peripheral blood involvement and lacked samples from very early time points of induction. DESIGN AND METHODS: In this study, we employed real-time quantitative polymerase chain reaction analysis to examine minimal residual disease in 398 pairs of blood and bone marrow follow-up samples taken from 95 children with B-cell precursor acute lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol. RESULTS: We confirmed the previously published poor correlation between minimal residual disease in blood and marrow at early treatment time points, with levels in bone marrow being higher than in blood in most samples (median 7.9-fold, range 0.04-8,293-fold). A greater involvement of peripheral blood at diagnosis was associated with a higher white blood cell count at diagnosis (P=0.003) and with enlargement of the spleen (P=0.0004) and liver (P=0.05). At day 15, a level of minimal residual disease in blood lower than 10(-4) was associated with an excellent 5-year relapse-free survival in 78 investigated patients (100% versus 69 ± 7%; P=0.0003). Subgroups defined by the level of minimal residual disease in blood at day 15 (high-risk: ≥ 10(-2), intermediate-risk: <10(-2) and ≥ 10(-4), standard-risk: <10(-4)) partially correlated with bone marrow-based stratification described previously, but the risk groups did not match completely. No other time point analyses were predictive of outcome in peripheral blood, except for a weak association at day 8. CONCLUSIONS: Minimal residual disease in peripheral blood at day 15 identified a large group of patients with an excellent prognosis and added prognostic information to the risk stratification based on minimal residual disease at day 33 and week 12.

• MeSH
• časové faktory MeSH
• dítě MeSH
• kojenec MeSH
• kostní dřeň metabolismus   patologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• mladiství MeSH
• pre-B-buněčná leukemie krev   diagnóza   farmakoterapie   patologie   MeSH
• předškolní dítě MeSH
• prognóza MeSH
• protokoly protinádorové kombinované chemoterapie aplikace a dávkování   MeSH
• reziduální nádor MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

BACKGROUND: Aberrant expression of myeloid antigens (MyAgs) on acute lymphoblastic leukemia (ALL) cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c -- Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases). METHODS: In a cohort of 365 consecutively diagnosed Czech B-precursor ALL patients, we analyze distribution of MyAg+ cases and mutual relationship among CD13, CD15, CD33, CD65 and CD66c. The most frequent MyAg (CD66c) is studied further regarding its stability from diagnosis to relapse, prognostic significance and regulation of surface expression. For the latter, flow cytometry, Western blot and quantitative RT-PCR on sorted cells is used. RESULTS: We show CD66c is expressed in 43% patients, which is more frequent than other MyAgs studied. In addition, CD66c expression negatively correlates with CD13 (p < 0.0001), CD33 (p = 0.002) and/or CD65 (p = 0.029). Our data show that different myeloid antigens often differ in biological importance, which may be obscured by combining them into "MyAg positive ALL". We show that unlike other MyAgs, CD66c expression is not shifted from the onset of ALL to relapse (n = 39, time to relapse 0.3-5.3 years). Although opposite has previously been suggested, we show that CEACAM6 transcription is invariably followed by surface expression (by quantitative RT-PCR on sorted cells) and that malignant cells containing CD66c in cytoplasm without surface expression are not found by flow cytometry nor by Western blot in vivo. We report no prognostic significance of CD66c, globally or separately in genotype subsets of B-precursor ALL, nor an association with known risk factors (n = 254). CONCLUSION: In contrast to general notion we show that different MyAgs in lymphoblastic leukemia represent different biological circumstances. We chose the most frequent and tightly genotype-associated MyAg CD66c to show its stabile expression in patients from diagnosis to relapse, which differs from what is known on the other MyAgs. Surface expression of CD66c is regulated at the gene transcription level, in contrast to previous reports.

• MeSH
• akutní lymfatická leukemie metabolismus   MeSH
• antigen CD33 MeSH
• antigen Lewis X biosyntéza   MeSH
• antigeny CD13 biosyntéza   MeSH
• antigeny diferenciační myelomonocytární biosyntéza   MeSH
• buněčná membrána metabolismus   MeSH
• časové faktory MeSH
• CD antigeny biosyntéza   MeSH
• cytoplazma metabolismus   MeSH
• dítě MeSH
• genetická transkripce MeSH
• genotyp MeSH
• glykosylace MeSH
• GPI-vázané proteiny MeSH
• imunofenotypizace MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• molekuly buněčné adheze biosyntéza   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• předškolní dítě MeSH
• přežití bez známek nemoci MeSH
• prognóza MeSH
• průtoková cytometrie MeSH
• recidiva MeSH
• regulace genové exprese u nádorů * MeSH
• RNA metabolismus   MeSH
• western blotting MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antigen CD33 MeSH
• antigen Lewis X MeSH
• antigeny CD13 MeSH
• antigeny diferenciační myelomonocytární MeSH
• CD antigeny MeSH
• CD33 protein, human MeSH Prohlížeč
• CD65s antigen, human MeSH Prohlížeč
• CEACAM6 protein, human MeSH Prohlížeč
• GPI-vázané proteiny MeSH
• molekuly buněčné adheze MeSH
• RNA MeSH