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H Hooijkaas

Publications and source records attributed to H Hooijkaas.

At least 37 records · Page 2Linked to original sources

[Immunology in medical practice. I. Introduction].

Fundamental immunology has seen a tremendous development in the past decades. This has resulted in a large body of knowledge, part of which has led to applications in laboratory diagnosis, but of which little has made its way to the clinic in terms of new therapies. The progress in understanding pathogenesis of diseases is also slow. This journal is planning a series of articles that highlight the recent achievements of immunology and their consequences for understanding and treating disease.

Allergy and Immunology↗

Analysis of variation in results of flow cytometric lymphocyte immunophenotyping in a multicenter study.

Fifty-five laboratories participated in a send-out study of four peripheral blood samples comparing a standard protocol vs. local protocols for flow cytometric lymphocyte immunophenotyping. The standard protocol included centrally provided reagents, instrument setup using triple-fluorescent microbeads and a three-color, whole-blood immunostaining technique based on fluorescein isothiocyanate and phycoerythrin-labeled monoclonal antibodies, erythrocyte lysis, washing, fixation, and identification of nucleated cells by the DNA/RNA stain LDS-751. Data analysis guidelines included lymphocyte selection using CD45,CD14-assisted "backgating" on forward (FSC) and sideward (SSC) light scatter and placement of fluorescence (FL) markers on the basis of the isotype control staining. Most (i.e., 77%) of the variation in results of percentage lymphocyte subset assessments using the standard protocol was explained by laboratory, sample, background FL, and the interaction between laboratory and sample. Purity and completeness of the FSC,SSC lymphogate, background FL, flow cytometer type, and flow cytometer setup (which were either partly or entirely determined by laboratory) contributed significantly to the variation. The effect of the leukocyte differential count on the variation in absolute numbers of lymphocyte subsets was particularly large in lymphopenic samples. The use of this standard protocol vs. local protocols did not reduce the interlaboratory variation. Instrument incompatibility with the standard protocol (e.g., incompatible filter combinations for LDS-751 detection) and lack of experience of many participants with three-color flow cytometry (in particular with the use of LDS-751) may have contributed to that result. We suggest that training and experience in a universally applicable standard protocol are critical for minimization of interlaboratory variation in flow cytometric immunophenotyping.

Antibodies, Monoclonal↗

Immunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations.

OBJECTIVE: Immunophenotyping of blood lymphocytes is an important tool in the diagnosis of hematologic and immunologic disorders. Because of maturation and expansion of the immune system in the first years of life, the relative and the absolute size of lymphocyte subpopulations vary during childhood. Therefore we wished to obtain reference values for the relative and the absolute size of all relevant blood lymphocyte subpopulations in childhood. STUDY DESIGN: We used the lysed whole blood method for analysis of lymphocyte subpopulations in 429 blood samples from neonates (n = 20), healthy children (n = 358), and adults (n = 51). The following age groups were used: 1 week to 2 months (n = 13), 2 to 5 months (n = 46), 5 to 9 months (n = 105), 9 to 15 months (n = 70), 15 to 24 months (n = 33), 2 to 5 years (n = 33), 5 to 10 years (n = 35), and 10 to 16 years (n = 23). RESULTS: Our results show that the absolute number of CD19+ B lymphocytes increases twofold immediately after birth, remains stable until 2 years of age, and subsequently gradually decreases 6.5-fold from 2 years to adult age. The CD3+ T lymphocytes increase 1.5-fold immediately after birth and decrease threefold from 2 years to adult age. The absolute size of the CD3+/CD4+ T-lymphocyte subpopulation follows the same pattern as the total CD3+ population, but the CD3+/CD8+ T lymphocytes remain stable from birth up to 2 years of age, followed by a gradual threefold decrease toward adult levels. In contrast to B and T lymphocytes, the absolute number of natural killer cells decreases almost threefold in the first 2 months of life and remains stable thereafter. Our study also showed that changes in the absolute size of lymphocyte subpopulations are not always consistent with changes in their relative size. This demonstrates that the relative counts of lymphocyte subsets do not reflect their actual size and are therefore of limited value. CONCLUSION: On the basis of this study we strongly recommend that immunophenotyping of blood lymphocytes for the diagnosis of hematologic and immunologic disorders be based on the absolute rather than on the relative size of lymphocyte subpopulations. Our data can be used as age-matched reference values for blood lymphocyte immunophenotyping.

Adolescent↗

Heterogeneity in junctional regions of immunoglobulin kappa deleting element rearrangements in B cell leukemias: a new molecular target for detection of minimal residual disease.

Virtually all immunoglobulin kappa (IGK) gene deletions are mediated via rearrangements of the so-called kappa deleting element (Kde). Kde rearrangements occur either to Vkappa gene segments (Vkappa-Kde rearrangements) or to the heptamer recombination signal sequence in the Jkappa-Ckappa intron. Kde rearrangements were analyzed by the polymerase chain reaction (PCR) and heteroduplex analysis in 130 B-lineage leukemias: 63 precursor-B-acute lymphoblastic leukemias (ALL) and 67 chronic B cell leukemias. To obtain detailed information about Kde rearrangements, we sequenced 109 of the 189 detected junctional regions. Vkappa gene family usage in the Vkappa-Kde rearrangements in our series of B-lineage leukemias was comparable to Vkappa gene family usage in functional Vkappa-Jkappa rearrangements in normal and malignant mature B cells, except for a higher frequency of VkappaII family usage in precursor-B-ALL. Junctional region sequencing of the Kde rearrangements in precursor-B-ALL revealed a mean insertion of 4.7 nucleotides and a mean deletion of 9.5 nucleotides, resulting in an extensive junctional diversity, whereas in chronic B cell leukemias the insertion (1.9) and deletion (6.0) were significantly lower. The relatively extensive junctional diversity of the Kde rearrangements in precursor-B-ALL allowed us to design leukemia/patient-specific oligonucleotide probes, which were proven to be useful for detection of minimal residual disease (MRD) with sensitivities of 10(-4) to 10(-5). Kde rearrangements occur in approximately 50% of precursor-B-ALL cases and are likely to remain stable during the disease course, because Kde rearrangements are assumed to be 'end-stage' rearrangements, which cannot easily be replaced by continuing rearrangement processes. These findings indicate that junctional regions of Kde rearrangements in precursor-B-ALL represent new valuable patient-specific PCR targets for detection of MRD.

Gene Deletion↗

Systemic and anti-neuronal auto-antibodies in patients with paraneoplastic neurological disease.

Sera from 23 patients with paraneoplastic disease of the central nervous system (PNS) were examined for the presence of anti-neuronal (anti-Hu, anti-Yo/PCA) and anti-Ri) and systemic auto-antibodies, including antibodies against DNA, centromeres, nRNP, Sm antigen, Scl-70, Ro(SS-A), La(SS-B), mitochondria, thyroid antigens, parietal calls, brush border antigen and rheumatoid factor. As controls, sera from 33 patients with small cell lung cancer, 33 with ovarian cancer and 7 with breast cancer and from 107 aged-matched healthy persons were used. Systemic auto-antibodies were found in 52% of patients with paraneoplastic neurological syndromes compared with only 16% (P = 0.001) in the control group with cancer only and 15% in the group of healthy controls. The relatively high percentage of systemic auto-antibodies in patients with PNS indicates that there is a genetic susceptibility to the development of auto-immune phenomena. This may provide an explanation for the relatively rare occurrence of PNS in patients with cancer.

Adult↗

Allergy to carbamazepine: parallel in vivo and in vitro detection.

PURPOSE: Five to 20% of patients discontinue antiepileptic drug (AED) therapy because of adverse reactions. Careful reintroduction, however, may be considered if true drug allergy can be ruled out. Definitive assessment of such immunologically mediated reactions requires demonstration of either specific antibodies or sensitized lymphocytes. METHODS: We investigated whether skin patch tests (PTs) and in vitro lymphocyte proliferation assays (LPAs) were suitable for detection of allergy to carbamazepine (CBZ) and the possibly cross-reactive oxcarbazepine (OCBZ). Data of 65 patients displaying a wide range of possibly allergic side effects to CBZ were available for analysis. Data of CBZ users without any side effects and healthy volunteers served as controls. Both PTs and LPAs were done with CBZ, OCBZ and three metabolites [CBZ-10,11-epoxide (CBZ-E), 10-monohydroxy-CBZ (MHD), and 10,11-dihydroxy-CBZ (DIOL)]. RESULTS: Positive PTs with CBZ were seen in 20% and with OCBZ in 14% of the patients. Positive LPA results with CBZ and OCBZ, respectively, were found in 40 and 19%. Both tests were positive in 14 and 7% of the patients. Cross-reactivity to OCBZ was seen in -40% of CBZ-reactive patients in both PTs and LPAs. CONCLUSION: These data illustrate the additional value of LPAs in the detection of CBZ allergy while showing that a major part of side effects to CBZ and OCBZ is not immunologically mediated, according to PTs and LPAs.

Adolescent↗

Flow cytometric detection of intracellular antigens for immunophenotyping of normal and malignant leukocytes.

Intracellular antigens are of major importance for immunophenotyping of normal leukocytes as well as leukemias and malignant lymphomas. Immunofluorescence microscopic evaluation of cytocentrifuge preparations has remained the preferred technique for detection of intracellular antigens for a long time. Recently, flow cytometric detection of intracellular antigens has been improved by the development of new permeabilization/fixation solutions. We compared four commercially available solutions: FACS Brand Lysing Solution (FACS Brand; Becton Dickinson, San Jose, CA, USA), Fix & Perm cell permeabilization kit (Fix & Perm; An der Grub, Vienna, Austria), OptiLyse B lysing solution (OptiLyse B; Immunotech, Marseille, France), and ORTHO PermeaFix(PermeaFix; Ortho Diagnostic Systems, Raritan, NJ, USA). These solutions were evaluated for the complexity and duration of the intracellular staining procedure, the effects on light scatter patterns, and the staining results for the intracellular antigens terminal deoxynucleotidyl transferase (TdT), cytoplasmic CD3 (CyCD3), myeloperoxidase (MPO), and cytoplasmic immunoglobulin light chains (CylgL). The four methods could easily be introduced in our laboratory and had only minor effect on the light scatter patterns of the tested cell samples. Each of the four tested antigens was detectable with at least one of the four methods. Only the Fix & Perm cell permeabilization kit could be used for reliable detection of all four intracellular antigens. In a large series of 450 BM and PB samples containing various percentages of TdT+ cells, the results of flow cytometric TdT staining with FACS Brand Lysing Solution were highly comparable to the results obtained by immunofluorescence microscopy (P = <0.00001). Our comparative study shows that flow cytometric detection of the intracellular antigens TdT, CyCD3, MPO, and CylgL can now reliably be performed on a routine basis.

Antigens↗

Detection of minimal residual disease in acute leukemia patients.

Diagnostic techniques, routinely used in clinical practice for monitoring acute leukemia patients, are able to detect only 1-5% of malignant cells. At present, two main techniques are being introduced for detection of minimal residual disease (MRD) in leukemia, namely immunological marker analysis and the polymerase chain reaction (PCR) technique with general sensitivity of 10(-4)-10(-5). Immunological marker analysis allows detection of unusual and aberrant immunophenotypes, and is usually performed by flow cytometry. PCR analysis allows detection of leukemia-specific DNA sequences, such as fusion regions of chromosome aberrations and junctional regions of rearranged immunoglogulin (Ig) genes and T-cell receptor (TcR) genes. The applicability of the immunophenotyping and PCR-mediated MRD techniques is dependent on the type of leukemia. In virtually all acute lymphoblastic leukemias, PCR analysis of Ig and TcR genes can be used, and immunophenotypic MRD detection is also possible in 70-80% of cases. In AML, immunophenotypic MRD detection can be applied in approximately 80% of cases and PCR analysis of chromosome aberrations in 25-40%. Each MRD technique has its advantages and limitations, which have to be weighed carefully to make an appropriate choice. Furthermore, standardization of the MRD techniques is needed before they are used for stratification or adaptation of treatment protocols. Finally, the clinical impact of MRD detection for the various subtypes of acute leukemias has to be established.

Acute Disease↗

Analysis of peripheral blood lymphocyte subsets, NK cells, and delayed type hypersensitivity skin test in patients with premature ovarian failure.

PROBLEM: Premature ovarian failure (POF) probably belongs to the group of autoimmune endocrinopathies. Cell-mediated immune parameters were investigated. Sex steroids have a profound effect on the immune system. POF patients and postmenopausal control women (PM) were tested with or without estrogen substitution. METHOD: A novel FACS analysis system (using double labeling techniques) was used in 30 patients with POF to enumerate the subjects of peripheral blood lymphocytes and NK cells. Eighteen PM women and 30 healthy men and women served as controls. We also tested the delayed type hypersensitivity skin test (DTH) toward Candida in the POF patient group to be informed on their cell-mediated immune function. RESULTS: The numbers of blood lymphocytes, CD3+, CD4+ and CD8+T cells, were not abnormal in POF patients. However, HLA-DR+T cells were increased in POF patients and in PM women (P < 0.05). These elevated numbers were partially reversible by estrogen substitution. The number of CD19+ cells (B cells) was elevated, whereas CD3-/CD16+/CD56+ cells (NK cells) were decreased in POF patients (P < 0.05), irrespective of estrogen substitution. DTH skin tests toward 0.1% Candidin (0.1 ml intradermal injection) were negative in 11 out of 20 tested POF patients, compared to only 2 out of 10 tested controls (P < 0.05). CONCLUSION: POF patients show numerous immune cell abnormalities. These abnormalities were only partially due to estrogen deficiency. We hypothesize that these abnormalities either lead to ovarian autoimmunity or may have direct effects on the ovarian function.

Adult↗

Immunologic effects of background prenatal and postnatal exposure to dioxins and polychlorinated biphenyls in Dutch infants.

Immunologic effects of pre- and postnatal polychlorinated biphenyl (PCB)/dioxin exposure in Dutch infants from birth to 18 mo of age are explored. The total study group consisted of 207 healthy mother-infant pairs, of which 105 infants were breast-fed and 102 children were bottle-fed. Prenatal PCB exposure was estimated by the PCB sum (PCB congeners 118, 138, 153, and 180) in maternal blood and the total toxic equivalent (TEQ) level in human milk (17 dioxin and 8 dioxin-like PCB congeners). Postnatal PCB/dioxin exposure was calculated as a product of the total TEQ level in human milk multiplied by the weeks of breast-feeding. The number of periods with rhinitis, bronchitis, tonsillitis, and otitis during the first 18 mo of life was used as an estimate of the health status of the infants. Humoral immunity was measured at 18 mo of age by detecting antibody levels to mumps, measles, and rubella. White blood cell counts (monocytes, granulocytes, and lymphocytes) and immunologic marker analyses CD4+ T-lymphocytes, CD8+ T-lymphocytes, activated T-lymphocytes (HLA-DR+CD3+), as well as T cell receptor (TcR) alpha beta+, TcR gamma delta+, CD4+CD45RA+ and CD4+CD45RO+ T-lymphocytes, B-lymphocytes (CD19+ and/or CD20+) and NK cells (CD16+ and/or CD56+/CD3-) in cord blood and venous blood at 3 and 18 mo of age were assessed in a subgroup of 55 infants. There was no relationship between pre- and postnatal PCB/dioxin exposure and upper or lower respiratory tract symptoms or humoral antibody production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Immunophenotypic changes between diagnosis and relapse in childhood acute lymphoblastic leukemia.

To get more insight into the phenotypic changes of childhood acute lymphoblastic leukemia (ALL) at relapse, a detailed morphological and immunophenotypic study in 40 childhood ALL cases (32 precursor B-ALL and 8 T-ALL) was performed. Expression patterns of non-lineage specific markers (terminal deoxynucleotidyl transferase (TdT), CD34, and HLA-DR), B-lineage markers (CD10, CD19, CD20, and CD22), T-lineage markers (CD1, CD2, CD3, CD4, CD5, CD7, and CD8), and cross-lineage myeloid markers (CD14, CD15, and CD33) were compared at diagnosis and relapse. In case of low blast counts (< or = 70%) at relapse, double labeling for membrane markers and TdT was used in order to define the precise immunophenotype of the TdT+ leukemic cells. An immunological marker-shift was defined as either a conversion from positive to negative and vice versa or a difference in positivity of > or = 50%. Morphological differences between diagnosis and relapse were detected in 34% of precursor B-ALL and 14% of T-ALL. Differences in immunological marker expression were found in 72% of precursor B-ALL and in 75% of T-ALL, and generally concerned minor shifts with loss or acquisition of a few markers. The morphological shifts and immunophenotypic shifts were not correlated. Immunophenotypic shifts were found for all markers tested in precursor B-ALL, except for HLA-DR. Shifts in CD10 expression (16% of cases) were only observed in relapses occurring 30 months or more after diagnosis. In four precursor B-ALL an intra-lineage shift was found at relapse (one common ALL to null ALL and three pre-B-ALL to common ALL or null ALL) and two precursor B-ALL cases were diagnosed as acute non-lymphocytic leukemia at relapse based on morphology and immunophenotype. In T-ALL, neither intra-lineage nor inter-lineage shifts were observed, although shifts were detected in all T cell markers tested, except for the lineage specific CD3 and T cell receptor (TcR) markers. In conclusion, immunophenotypic shifts at relapse frequently occur in precursor B-ALL and T-ALL, in a small percentage leading to an intra-lineage shift (10%) or inter-lineage shift (5%). Therefore immunophenotypic monitoring of minimal residual disease in ALL patients should be based on multiple marker combinations, preferably together with polymerase chain reaction analysis of rearranged immunoglobulin and/or TcR genes or chromosome aberrations.

Adolescent↗

Analysis of Ig and T-cell receptor genes in 40 childhood acute lymphoblastic leukemias at diagnosis and subsequent relapse: implications for the detection of minimal residual disease by polymerase chain reaction analysis.

The rearrangement patterns of Ig and T-cell receptor (TcR) genes were studied by Southern blot analysis in 30 precursor B-cell acute lymphoblastic leukemias (B-ALLs) and 10 T-ALLs at diagnosis and subsequent relapse. Eight precursor B-ALLs appeared to contain biclonal/oligoclonal Ig heavy-chain (IgH) gene rearrangements at diagnosis. Differences in rearrangement patterns between diagnosis and relapse were found in 67% (20 cases) of precursor B-ALLs (including all eight biclonal/oligoclonal cases) and 50% (five cases) of T-ALLs. In precursor B-ALLs, especially changes in IgH and/or TcR-delta gene rearrangements were found (17 cases), but also changes in TcR-beta, TcR-gamma, Ig kappa, and/or Ig lambda genes (11 cases) occurred. The changes in T-ALLs concerned the TcR-beta, TcR-gamma, TcR-delta, and/or IgH genes. Two precursor B-ALLs showed completely different Ig and TcR gene rearrangement patterns at relapse, suggesting the absence of a clonal relation between the leukemic cells at diagnosis and relapse and the development of a secondary leukemia. The clonal evolution in the other 23 ALL patients was based on continuing rearrangement processes and selection of subclones. The development of changes in Ig and TcR gene rearrangement patterns was related to remission duration, suggesting an increasing chance of continuing rearrangement processes with time. These immunogenotypic changes at relapse occurred in a hierarchical order, with changes in IgH and TcR-delta genes occurring after only 6 months of remission duration, whereas changes in other Ig and TcR genes were generally detectable after 1 to 2 years of remission duration. The heterogeneity reported here in Ig and/or TcR gene rearrangement patterns at diagnosis and relapse might hamper polymerase chain reaction (PCR)-mediated detection of minimal residual disease (MRD) using junctional regions of rearranged Ig or TcR genes as PCR targets. However, our data also indicate that in 75% to 90% of ALLs, at least one major rearranged IgH, TcR-gamma, or TcR-delta band (allele) remained stable at relapse. We conclude that two or more junctional regions of different genes (IgH, TcR-gamma, and/or TcR-delta) should be monitored during follow-up of ALL patients for MRD detection by use of PCR techniques. Especially in biclonal/oligoclonal precursor B-ALL cases, the monitoring should not be restricted to rearranged IgH genes, but TcR-gamma and/or TcR-delta genes should be monitored as well, because of the extensive changes in IgH gene rearrangement patterns in this ALL subgroup.

Adolescent↗

The presence of peptidoglycan-polysaccharide complexes in the bowel wall and the cellular responses to these complexes in Crohn's disease.

Interestingly, using a monoclonal antibody, peptidoglycan-polysaccharide complexes (PPC) were detected intracellularly in the mucosa and submucosa of the bowel wall of Crohn's disease (CD) patients. PPC are the main constituents of the gram-positive bacterial cell wall. These PPC were however detected in the normal bowel wall also. Therefore, in this study the hypothesis that an enhanced immune responsiveness to bacterial antigens plays a pivotal role in the induction or the chronicity of CD was tested. As antigens, the peptidoglycan structures of intestinal bacteria (Eubacterium aerofaciens or fecal PPC) or of Streptococcus pyogenes, the 65-kDa heat shock protein and muramyl dipeptide (MDP), the smallest bioactive subunit of peptidoglycan, were used. The proliferative responses of peripheral blood (PB) mononuclear cells (MNC) of healthy subjects and patients in a remissive stage of CD or an active CD stage were examined. Of this last patient group the MNC responses of the mesenterial lymph nodes that drain the inflamed gut area were measured also. The responses of PB-MNC of the healthy subjects and the patients in a remissive CD stage were not different. Compared to the responses in remissive CD, the PB-MNC responses in active CD to the eubacterial cell wall and streptococcal cell wall antigen were significantly higher. At the inflammation site in active CD, the lymph nodes, the responses to most of the bacterial antigens were significantly higher than in the PB. In summary, the results show the presence of bacterial peptidoglycan in the bowel wall and the immune responsiveness, especially at the inflammation site, to these antigens in active CD and therefore present suggestive evidence for the role of peptidoglycan in the etiology and/or pathogenesis of CD.

Adult↗

[111In-DTPA-D-Phe1] octreotide scintigraphy in thyroidal and orbital Graves' disease: a parameter for disease activity?

Visualization of malignant lymphomas and granulomatous disease is possible by [111In-DTPA-D-Phe1]octreotide scintigraphy through binding of the radioligand to somatostatin receptors on activated leukocytes. Because thyroidal and orbital tissues are infiltrated by activated leukocytes in Graves' disease, a cross-sectional study to visualize disease activity with [111In-DTPA-D-Phe1]octreotide scintigraphy was performed. A correlation between thyroidal [111In-DTPA-D-Phe1]octreotide accumulation and free T4 (disease expression) and thyroid binding-inhibiting immunoglobulins (disease activity) is present in untreated hyperthyroid Graves' disease. There is also a correlation between orbital [111In-DTPA-D-Phe1]octreotide uptake and the clinical activity score (disease activity) and total eye score (disease expression), respectively, in Graves' orbitopathy. Visualization of thyroidal and orbital Graves' disease is feasible, but further investigation is necessary to establish the role of [111In-DTPA-D-Phe1]octreotide scintigraphy in representing disease activity and expression and in predicting therapeutical outcome.

Eye↗

Immunohistochemical characterization of monocytes-macrophages and dendritic cells involved in the initiation of the insulitis and beta-cell destruction in NOD mice.

This immunohistochemical study describes the infiltration pattern of monocytes-macrophages and dendritic cells during the development of insulitis and diabetes in the NOD mouse. A panel of monoclonal antibodies (MoAbs) was used to analyze pancreases of nondiabetic (glucosuria negative) male and female NOD mice at 3, 7, 10, and 17 weeks of age. BALB/c female mice 17-weeks-old, diabetic NOD female mice 20- to 30-weeks-old, and nondiabetic NOD male mice 22-weeks-old were used as controls. Three MoAbs (viz., ER-MP23, MOMA1, and BM8) were special and appeared to identify macrophage/dendritic cell subsets that either had a characteristic infiltration pattern in the initial phases of the autoimmune reaction before T-cell infiltration or were typical for the later beta-cell destructive insulitis process. 1) Raised numbers of ER-MP23+ and MOMA-1+ dendritic cells/macrophages were characteristic for the initial phases of the NOD insulitis in 3-week-old mice. The cells were found in and near swollen para-insular vessels. In 7-week-old mice, these ER-MP23+ and MOMA-1+ cells had accumulated around the islets and were the first hematopoietic cells detectable at these spots. 2) From 7 weeks of age onward, BM8+ macrophages could be found in the para- and peri-insulitis processes. However, only in females were these BM8+ macrophages found to infiltrate into the islets. In lymphoid tissues, ER-MP23 predominantly reacts with macrophages/dendritic cells present in the subcapsular and interfollicular sinuses of lymph nodes and the T-cell zones of these lymph nodes. ER-MP23 also reacts with tissue macrophages/dendritic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

12p chromosomal aberrations in precursor B childhood acute lymphoblastic leukemia predict an increased risk of relapse in the central nervous system and are associated with typical blast cell morphology.

Recently we reported cytogenetic, clinical, and immunologic data of 135 childhood ALL patients, who were diagnosed and treated in The Sophia Children's Hospital between January 1, 1980 and November 1, 1990. An increased risk for a first relapse in the central nervous system (CNS) was detected in a subgroup of childhood ALL patients with common ALL or pre-B ALL phenotype and chromosomal aberrations of the short arm of chromosome 12. In this paper we report clinical, cytogenetic, immunologic, morphologic and cytochemical data on these eight childhood ALL patients with aberrations of the short arm of chromosome 12 and of an additional four cases that were diagnosed and treated between November 1, 1990 and February 1, 1992. We found that three out of six common ALL, two out of three pre-B ALL and one out of three T-ALL patients with 12p chromosomal rearrangements developed a first relapse in the CNS. On the contrary, the frequency of CNS relapse in our childhood ALL patients without 12p aberrations was 10%. Furthermore, morphologic and cytochemical analysis of the bone marrow smears of these 12 patients with aberrations of the short arm of chromosome 12 revealed that the nine cases with pre-B or common ALL phenotype had typical morphologic characteristics that are unusual for newly diagnosed childhood ALL. Typical for this subtype is the presence of large polymorphic blast cells without nucleoli. The nuclei are irregularly shaped showing folds and clefts and a stripy pattern. The nucleus and cytoplasm are often abundantly vacuolated. The cytoplasm has a foamy light-blue appearance.

Adolescent↗