Alicja Sonsala

The Immunophenotypes of Blast Cells in B-Cell Precursor Acute Lymphoblastic Leukemia: How Different Are They from Their Normal Counterparts?

Currently, there are three major maturational stages of CD19 antigen expressing B‐cell precursors (hematogones). In B‐cell precursor acute lymphoblastic leukemia (BCP‐ALL), the malignant counterpart of hematogones, the leukemic blasts share common phenotypic features. The aim of the study was to enumerate the actual differences between the leukemic blasts in the CD10+ and CD10− subgroups of BCP‐ALL and hematogones by assessing the expression of the antigens: TdT, CD34, CD45, CD10, CD38, CD20 and CD22.

Subpopulacje limfocytów T i komórek NK we krwi obwodowej u zdrowych dzieci w wieku 3–19 lat

Streszczenie Wstep Ocena poszczegolnych subpopulacji komorek linii limfocytarnej krwi obwodowej ma istotne znaczenie w diagnostyce wielu zaburzen u dzieci. Analiza wynikow i mozliwośc oceny zmian w ukladzie limfoidalnym wymaga znajomości wartości odsetkowych i liczbowych poszczegolnych linii limfocytow określonych dla zdrowej populacji. Cel Celem aktualnej pracy bylo dokladne określenie wartości odsetkowych oraz bezwzglednych komorek ukladu limfoidalnego (subpopulacje linii limfocytow T i NK) we krwi obwodowej w populacji dzieci zdrowych. Material i metoda Badania wykonano za pomocą 6-kolorowej cytometrii przeplywowej u 40 zdrowych dzieci w wieku 3–19 lat. Wyniki Przedstawione w niniejszym opracowaniu mogą posluzyc jako odniesienie do celow kontrolno-porownawczych dla wynikow pacjentow z zaburzeniami w ukladzie immunologicznym w przebiegu roznego typu schorzen. Jest to pierwsza w Polsce publikacja w tak szeroki sposob określająca rozklad wybranych subpopulacji komorek jednojądrzastych krwi obwodowej u dzieci.

Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL

Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07–5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05–3.52, P = 0.03, MRD-day33 and MRD-week12, P < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02–5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28–12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61–28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL.

Ekspresja receptorów dla chemokin na subpopulacjach limfocytów T we krwi obwodowej u zdrowych dzieci

Streszczenie Uklad chemokiny–receptory odgrywa zasadniczą role w calej embriogenezie, reguluje takze procesy wrodzonej i nabytej odporności, co prowadzi do wytworzenia prawidlowej odpowiedzi immunologicznej. Analiza wynikow i mozliwo ści oceny zmian w ukladzie limfoidalnym wymaga znajomości wartości odsetkowych i liczbowych poszczegolnych linii limfocytow określonych dla zdrowej populacji. Cel Celem aktualnej pracy bylo dokladne określenie wartości odsetkowych oraz bezwzglednych antygenow powierzchniowych limfocytow T, bedących receptorami dla wybranych chemokin, we krwi obwodowej w populacji dzieci zdrowych, przy wykorzystaniu wielokolorowej cytometrii przeplywowej, a takze porownanie uzyskanych wartości w badanej grupie z uwzglednieniem plci i wieku. Wyniki Wyniki przedstawione w niniejszej pracy mogą posluzyc jako odniesienie do wynikow uzyskanych u pacjentow z zaburzeniami ukladu immunologicznego w przebiegu roznych schorzen. Jest to pierwsza w Polsce publikacja w tak szeroki sposob określająca rozklad subpopulacji limfocytow T krwi obwodowej u dzieci z receptorami dla wybranych chemokin.

Surface expression of Cytokine Receptor-Like Factor 2 increases risk of relapse in pediatric acute lymphoblastic leukemia patients harboring IKZF1 deletions

We prospectively examined whether surface expression of Cytokine Receptor-Like Factor 2 (CRLF2) on leukemic blasts is associated with survival and induction treatment response in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients. Flow cytometric analysis of bone marrow-derived leukemia cells revealed that 7.51% (29/286) of 386 pediatric BCP-ALL patients were CRLF2-positive (CRLF2pos) at diagnosis. The median minimal residual disease (MRD) was lower in CRLF2pos than CRLF2-negative (CRLF2neg) patients on day 15 (MRD15) after induction therapy [0.01% (0.001-0.42%) vs. 0.45% (0.05-3.50%); p=0.001]. By contrast, the MRD15 was higher in Ikaros family Zinc Finger Protein 1 (IKZF1)-deleted BCP-ALL patients than in BCP-ALL patients without IKZF1 deletions [1.18% (0.06-12.0%) vs 0.33% (0.03-2.6%); p=0.003]. Subgroup analysis showed that MRD15 levels were lower in IKZF1Δ/CRLF2pos patients than in IKZF1Δ/CRLF2neg patients [0.1% (0.02-5.06%) vs. 2.9% (0.25-12%); p=0.005]. Furthermore, MRD15 levels were higher in IKZF1WT/CRLF2neg patients than in IKZF1WT/CRLF2pos patients [0.40% (0.04-2.7%) vs. 0.001% (0.001-0.01%)]. Despite the low MRD15 levels, IKZF1Δ/CRLF2pos patients showed poorer relapse-free survival (RFS) than other patient groups (p=0.003). These findings demonstrate that surface CRLF2 expression is associated with increased risk of relapse in pediatric BCP-ALL patients harboring IKZF1 deletions.

Cost-effective screening of DNMT3A coding sequence identifies somatic mutation in pediatric T-cell acute lymphoblastic leukemia

In pediatric T‐cell acute lymphoblastic leukemia (T‐ALL), risk assignment schemes preclude reliable prediction of outcome, and thus, new prognostic factors are needed. Mutations in DNMT3A are candidate prognostic and classification markers in adults with acute myeloid leukemia (AML) and T‐ALL and thus were considered as candidates prognostic markers in pediatric T‐ALL.

Clinical immunology Quantitative changes of NK cells in umbilical cord blood of neonate in relation to the mode of delivery

Introduction: Natural killer (NK) cells are an important element connecting innate and acquired resistance in humans. They can be detected in fetal liver since the 6 th week of pregnancy and in the sec ond half of pregnancy the number increases to values observed in adults. The main aim of the study was the assessment of the NK cells and defining a relationship between the mode of delivery and NK cells quantitative changes in umbilical cord blood. Material and methods: The study included 72 neonates. Taking into consideration the time and mode of delivery, the children were divided into following groups. Group I included 40 full term neonates: 17 neonates born vaginally and 23 by cesarean section. Group II included 32 near-term neonates: 6 neonates born vaginally, 26 by cesarean section. Assessment of NK cells was performed with a flow cytometry technique. Results: It was shown that the percentage NK cells’ of in all full term neonates was statistically high er than in near-term ones. A higher mean percentage of those cells was also shown in full term and nearterm neonates born by cesarean section. The mean number of NK cells lymphocytes in full term neonates born by elective cesarean section was statistically significantly lower than in neonates born by emer gency cesarean section. Conclusion: Cesarean section can be related to significant quantitative changes in NK cells in the umbilical cord blood. Near-term neonates, regardless of the mode of delivery, show lower values of NK cells in umbilical blood. Elective cesarean section carried out at term can be a cause of decrease of mean number of NK cells in neonate umbilical blood.