Oxidative stress and reactive nitrogen species generation during renal ischemia.

Previous evidence suggests that both oxygen radicals and nitric oxide (NO) are important mediators of injury during renal ischemia-reperfusion (I-R) injury. However, the generation of reactive nitrogen species (RNS) has not been evaluated in this model at early time points. The purpose of these studies was to examine the development of oxidant stress and the formation of RNS during I-R injury. Male Sprague-Dawley rats were anesthetized and subjected to 40 min of bilateral renal ischemia followed by 0, 3, or 6 h of reperfusion. Control animals received a sham operation. Plasma urea nitrogen and creatinine levels were monitored as markers of renal injury. Glutathione (GSH) oxidation and 4-hydroxynonenal (4-HNE)-protein adducts were used as markers of oxidant stress. 3-Nitrotyrosine (3-NT) was used as a biomarker of RNS formation. Significant increases in plasma creatinine concentrations and urea nitrogen levels were found following both 3 and 6 h of reperfusion. Increases in GSH oxidation, 4-HNE-protein adduct levels, and 3-NT levels were observed following 40 min of ischemia with no reperfusion. Since these results suggested RNS generation during the 40 min of ischemia, a time course of RNS generation following 0, 5, 10, 20, and 40 min of ischemia was evaluated. Significant increases in 3-NT generation was detected as early as 10 min of ischemia and rose to values nearly 10-fold higher than Control at 40 min of ischemia. No additional increase was observed following reperfusion. The data clearly demonstrate that oxidative stress and RNS generation occur in the kidney during ischemia.

Nicotinic regulation of c-fos and osteopontin expression in human-derived osteoblast-like cells and human trabecular bone organ culture.

Long-term in vivo studies have highlighted smoking as a risk factor in postmenopausal osteoporosis, bone fracture incidence, and increased nonunion rates. In contrast, there are few data postulating the effects of smoking at the cellular level in human skeletal tissue. In this study, we present novel evidence demonstrating that the nicotinic receptor alpha4 subunit is present in human primary bone cells by using reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, we demonstrate direct cellular effects of nicotine on primary human bone cells and blockage of these effects with a nicotinic receptor antagonist, D-tubocurarine. Nicotine effects on cell proliferation were biphasic with toxic, antiproliferative effects at high levels of nicotine (>1 mmol/L) and stimulatory effects at very low levels (0.01-10 micromol/L) after 72 h. This nicotine-induced increase in cell proliferation was inhibited in a dose-dependent manner by the addition of D-tubocurarine. In addition, proliferation effects from low-level treatment correlated with an upregulation of expression of the AP-1 transcription factor, c-fos, within 1 h, which was blocked by incubation with D-tubocurarine. To determine in situ bone cell responses within their trabecular matrix, cores of human bone isolated from biopsies were perfused with 0.1 micromol/L nicotine for 24 h. Western analysis of proteins isolated from the cores highlighted an increase in osteopontin, a bone matrix protein implicated in regulating resorption, which was partially inhibited by the addition of D-tubocurarine. To conclude, our results suggest that nicotine has a direct effect on human bone cells in modulating proliferation, upregulation of the c-fos transcription factor, and the synthesis of the bone matrix protein, osteopontin.

Evidence for peroxynitrite formation in renal ischemia-reperfusion injury: studies with the inducible nitric oxide synthase inhibitor L-N(6)-(1-Iminoethyl)lysine.

Reactive oxygen species are suggested to participate in ischemia-reperfusion (I-R) injury. However, induction of inducible nitric oxide synthase (iNOS) and production of high levels of nitric oxide (NO) also contribute to this injury. NO can combine with superoxide to form the potent oxidant peroxynitrite (ONOO(-)). NO and ONOO(-) were investigated in a rat model of renal I-R injury using the selective iNOS inhibitor L-N(6)-(1-iminoethyl)lysine (L-NIL). Sprague-Dawley rats were subjected to 40 min of bilateral renal ischemia followed by 6 h of reperfusion with or without L-NIL administration. Control animals received a sham surgery and had plasma creatinine values of 0.4 +/- 0.1 mg/dl. I-R surgery significantly increased plasma creatinine levels to 1.9 +/- 0.3 mg/dl (P <.05) and caused renal cortical necrosis. L-NIL administration (3 mg/kg) in animals subjected to I-R significantly decreased plasma creatinine levels to 1.2 +/- 0.10 mg/dl (P <.05 compared with I-R) and reduced tubular damage. ONOO(-) formation was evaluated by detecting 3-nitrotyrosine-protein adducts, a stable biomarker of ONOO(-) formation. Immunohistochemistry and HPLC revealed that the kidneys from I-R animals had increased levels of 3-nitrotyrosine-protein adducts compared with control animals. L-NIL-treated rats (3 mg/kg) subjected to I-R showed decreased levels of 3-nitrotyrosine-protein adducts. These results support the hypothesis that iNOS-generated NO mediates damage in I-R injury possibly through ONOO(-) formation.

Oxidant stress in rat liver after lipopolysaccharide administration: effect of inducible nitric-oxide synthase inhibition.

The role of inducible nitric-oxide synthase (iNOS) in lipopolysaccharide (LPS)-induced hepatic oxidant stress was evaluated using the iNOS inhibitor L-iminoethyl-lysine (L-NIL). Male rats were divided into three groups. One group received LPS (Salmonella minnesota) 2 mg/kg i.v. A second group received LPS plus L-NIL (3 mg/kg i.p.) at the time of LPS administration followed by a second dose 3 h later. A third group received saline i.v. At 6 h, blood and liver tissue were collected. Serum nitrate/nitrite (metabolic products of nitric oxide) levels were increased from 5.4 +/- 1.5 nmol/ml in the saline group to 360 +/- 48 nmol/ml in the LPS group (n = 5). Values for the LPS + L-NIL group were significantly reduced to 35 +/- 7 nmol/ml. Tissue malondialdehyde levels were increased from 0.20 +/- 0.02 nmol/mg (n = 4) in the saline group to 0.41 +/- 0.03 nmol/mg (n = 4) in the LPS group. L-NIL significantly reduced the values in the LPS group to 0.29 +/- 0.02 nmol/mg (n = 4). 4-Hydroxynonenal-protein adducts levels were increased 3.6-fold by LPS treatment as compared with saline. L-NIL significantly reversed the levels to 1.6-fold (n = 4). Intracellular GSH levels were decreased from 8.49 +/- 0.64 nmol/mg (n = 4) in the saline group to 5.63 +/- 0.51 nmol/mg in the LPS group (n = 7). L-NIL significantly increased the levels in the LPS group to 7.04 +/- 0.46 nmol/mg (n = 7). These data indicate that LPS-induced nitric oxide generation can result in oxidant stress in the liver, and that inhibitors of iNOS may offer some protection in LPS-induced hepatic toxicity.

Role of nitric oxide in lipopolysaccharide-induced oxidant stress in the rat kidney.

Lipopolysaccharide (LPS)-induced renal oxidant injury and the role of nitric oxide (NO) were evaluated using the inducible nitric oxide synthase (iNOS) inhibitor L-iminoethyl-lysine (L-NIL). One group of male rats received LPS (Salmonella minnesota; 2 mg/kg, i.v.). A second group received LPS plus L-NIL (3 mg/kg, i.p.). A third group received saline i.v. At 6 hr, iNOS protein was induced in the kidney cortex, and plasma nitrate/nitrite levels were increased from 4 +/- 2 nmol/mL in the Saline group to 431 +/- 23 nmol/mL in the LPS group. The value for the LPS + L-NIL group was reduced significantly to 42 +/- 9 nmol/mL. LPS increased blood urea nitrogen levels from 13 +/- 1 to 47 +/- 3 mg/dL. LPS + L-NIL reduced these levels significantly to 29 +/- 2 mg/dL. Plasma creatinine levels were unchanged in all groups. Tissue lipid peroxidation products in the kidney were increased from 0.16 +/- 0.01 nmol/mg in the Saline group to 0.30 +/- 0.03 nmol/mg in the LPS group. LPS + L-NIL reduced the values significantly to 0.22 +/- 0.02 nmol/mg. Intracellular glutathione levels were decreased in the kidneys from 1.32 +/- 0.1 nmol/mg in the Saline group to 0.66 +/- 0.08 nmol/mg in the LPS group. LPS + L-NIL increased the levels significantly to 0.99 +/- 0.13 nmol/mg. LPS increased the 3-nitrotyrosine-protein adducts in renal tubules as detected by immunohistochemistry, indicating the generation of peroxynitrite. L-NIL decreased adduct formation. These data indicated that LPS-induced NO generation resulted in peroxynitrite formation and oxidant stress in the kidney and that inhibitors of iNOS may offer protection against LPS-induced renal toxicity.

Monosomy 20 as a pointer to dicentric (9;20) in acute lymphoblastic leukemia.

Twenty new cases of acute lymphoblastic leukemia (ALL) with the dicentric chromosome dic(9;20)(p1113;q11) are presented. This chromosomal abnormality is difficult to identify from G-banding alone. It masquerades as monosomy 20 and is only accurately identified by fluorescence in situ hybridization (FISH). Monosomy 20 was found in 59/2790 patients with successful karyotypes entered to the Leukaemia Research Fund/UK Cancer Cytogenetics Group Karyotype Database in ALL (LRF/UKCCG Karyotype Database). FISH revealed dic(9;20) in 20/25 cases with available material. Extra copies of chromosome 21 were found in 8 of the 20 cases. Patients were 14 females and six males, aged 1-32 years (median 4 years), with leukocyte counts of 2-536 (median 23) x 109/l and immunophenotypes of common or pre-B ALL (17 cases), T-ALL (one case) or unknown (two cases). Four patients relapsed at 2, 22, 28 and 47 months and two died at 49 and 63 months (median follow-up 37 months). FISH studies on the remaining five patients showed one with monosomy 20 and four with other rearrangements of the chromosome. This study has increased the number of reported cases of dic(9;20) from 17 to 37. It has identified dic(9;20) in one case of T-ALL and shows an association of this translocation with trisomy 21.

Investigation of clonal involvement of myeloid cells in Philadelphia-positive and high hyperdiploid acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) with a high hyperdiploid clone has a good prognosis for both childhood and adult patients while patients with Philadelphia-positive (Ph) ALL do badly at all age groups. It has been suggested that different responses to treatment might be related to the cell of origin of the leukemia with 'stem cell' cases responding less well than those arising in a lymphoid committed progenitor cell. The clonal involvement of different cell lineages in 12 patients with acute lymphoblastic leukemia has been examined by applying fluorescence in situ hybridization (FISH) to detect chromosomal abnormalities in bone marrow cells previously identified by morphology and/or immunology. The karyotype of the malignant clone was either high hyperdiploid or Philadelphia translocation (Ph) positive with a breakpoint in the minor breakpoint cluster region of the BCRgene (m-BCR) or in the major breakpoint cluster region of the BCR gene (M-BCR). The high hyperdiploid clone, in each case, was found in cells of the B-lymphoid (CD19+) lineage but not in T cells (CD3+) or in cells of the myeloid (CD13+) or erythroid (glycophorin A+) lineages, indicative of a lymphoid committed progenitor cell. Heterogeneity of lineage involvement was found in Ph+ ALL: the m-BCR Ph+ clone was found in lymphoid/blast cells but not in neutrophils or eosinophils. In contrast both M-BCR Ph+ clones were detected in myeloid as well as lymphoid lineages, indicative of a stem cell origin.

Radiographic, ultrasonographic, and endoscopic findings in cats with inflammatory bowel disease of the stomach and small intestine: 33 cases (1990-1997).

OBJECTIVE: To characterize imaging findings in cats with confirmed inflammatory bowel disease (IBD) of the upper gastrointestinal tract (i.e., stomach and small intestine) and relate these findings to clinical signs and histologic changes. DESIGN: Retrospective study. ANIMALS: 32 cats with clinical and histopathologic diagnoses of IBD. PROCEDURE: Medical records were reviewed for signalment, clinical signs, clinicopathologic findings, radiographic and ultrasonographic findings, and results of endoscopic examination. Histologic findings were reviewed and characterized by severity and type of inflammatory infiltrate. RESULTS: All cats had 1 or more clinical signs (e.g., vomiting, diarrhea, weight loss, and anorexia) consistent with IBD. Lymphocytic and plasmacytic infiltrates were observed in histologic sections of gastrointestinal tissue. Crypt distortion, villous blunting and fusion, and fibrosis were most commonly seen in cats with moderate or severe IBD. Clinicopathologic findings of some cats included anemia, leukocytosis or leukopenia, hypocholesterolemia, and hyper- or hypoproteinemia. Abnormalities were not found on abdominal radiographic views in 9 of 9 cats. However, contrast studies using barium revealed radiographic abnormalities in 1 of 3 cats. In 13 of 17 cats, abdominal ultrasonography revealed several intestinal abnormalities (e.g., poor intestinal wall layer definition, focal thickening) and large mesenteric lymph nodes with hypoechoic changes consistent with IBD. Endoscopic observation revealed findings (e.g., erythema, plaques, mucosal friability) consistent with inflammation in 9 of 18 cats. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with endoscopy of the gastrointestinal tract or abdominal radiography, clinical signs and ultrasonographic findings appear to have the best association with histologic grade of IBD in cats.

The importance of cytogenetics and associated molecular techniques in the management of patients with leukaemia.

The cytogenetic analysis of haematological malignancies plays a major role in diagnosis. A large number of non-random chromosomal abnormalities are associated with specific types of leukaemia. Often, the cytogenetic result provides the definitive diagnosis. The recent developments in molecular cytogenetic technologies, in association with conventional cytogenetic analysis, have improved the accuracy of the results and led to the finding of new chromosomal abnormalities in leukaemia. Patients may be monitored by cytogenetics, molecular techniques and/or fluorescence in situ hybridization (FISH) during the course of their management, for evidence of minimal residual disease. These techniques also provide a useful method for monitoring patients following bone marrow transplantation, particularly when the patient and the donor are of the opposite sex. The cytogenetic result is an independent prognostic indicator, with certain karyotypes associated with a good prognosis, although others indicate a poor outcome.

Bilateral perinephric pseudocysts and polycystic kidneys in a ferret.

A 3-year-old castrated male domestic ferret was evaluated for abdominal distention. Survey lateral and dorsoventral abdominal radiographs were made. There were two soft tissue radiopacities consistent with grossly enlarged kidneys displacing small bowel and colon cranially, ventrally and caudally. Abdominal ultrasound was performed and revealed bilateral perinephric pseudocysts and polycystic kidneys. The perinephric pseudocysts were found to be dilated renal capsules on exploratory surgery and were drained. On follow up examinations, the pseudocysts were drained by ultrasound-guided paracentesis. The perinephric cyst fluid was distinguished from urine by measuring creatinine concentration and plans were made to resect the renal capsules due to rapid re-accumulation of pseudocyst fluid. The ferret's condition deteriorated and euthanasia was performed. Post-mortem examination was declined by the owner. Perinephric pseudocysts are rare and this is the first published report in a ferret. Ultrasound examination is the most rapid, accurate and non-invasive method for diagnosis of perinephric pseudocysts.

Abnormalities of the ETV6 gene occur in the majority of patients with aberrations of the short arm of chromosome 12: a combined PCR and Southern blotting analysis.

Involvement of the ETV6 gene, located at 12p13, has been investigated in 20 patients with an abnormality of the short arm of chromosome 12 (abn 12p) detected cytogenetically. Patients in the study had c/pre-B acute lymphoblastic leukemia (ALL) (nine children and three adults), T-ALL (three adults), acute myeloid leukemia (AML) (two adults), biphenotypic acute leukemia (Bip-L) (one adult), myelodysplasia (MDS) (one adult) and chronic myelomonocytic leukemia (CMML) (one child). Abnormalities of 12p comprised deleted (del)(12p) alone (seven cases), add(12p) alone (seven cases), del(12p) and add(12p) (one case) and balanced translocations of 12p to 1p13, 1q31, 10q11, 14q11 and 15q15 (one case of each). A novel, exon-specific RT-PCR assay identified breakpoints in ETV6 in nine of 19 cases, and showed breakpoints in intron 5 (seven cases of children with c-ALL), in intron 4 (in one adult with Bip-L) and in intron 2 (in one adult with AML). RT-PCR for the ETV6/AMLI fusion (tested in 19 cases) was positive using standard primers in five cases (four of which had shown rearrangements in intron 5) and occurred as a variant fusion in a sixth case (also positive for a rearrangement in intron 5) using 3' RACE PCR. Southern blotting confirmed rearrangements in intron 5 in the five cases available for analysis and revealed a rearrangement in intron 5 in one of 10 cases with no evidence of intron 5 involvement by RT-PCR. Rearrangements in intron 5 of ETV6 were found in eight of nine cases of children with c-ALL of which six carried the ETV6/AMLI fusion. Heterozygosity within intron 5 (revealed by the genomic probe B1) was found in seven of 11 cases tested. Deletion of one allele was indicated in three cases with del(12p) and one case with add(12p). This study, using a combination of ETV6 exon-specific RT-PCR, RT-PCR for ETV6/AMLI and Southern blotting has shown that rearrangement and/or deletion of ETV6 may occur in up to 70% of patients with abn 12p. Furthermore, 90% of children in this study with an abn 12p and c-ALL, carried a rearrangement of ETV6 in intron 5.

Trisomy 13 and myeloid malignancy--characteristic blast cell morphology: a United Kingdom Cancer Cytogenetics Group survey.

We retrospectively report data on 28 patients with haematological malignancy and trisomy 13 (25 cases) or tetrasomy 13 (three cases) as the primary acquired cytogenetic change. Peripheral blood and/or bone marrow morphology was reviewed in 25/28 cases and the final diagnosis was as follows: AML M0 (11), AML M1 (6), AML M2 (2), AML M4 (2), AML M5b (1), AML M6 (1), RAEB-t (3), RAEB (1), RA (1). All three cases with tetrasomy 13 had AML M0. Characteristic small hand-mirror blasts with cytoplasmic blebs and tails and scanty small granules were seen in 13/25 cases and 18/25 cases had small blasts which could easily be mistaken for lymphoblasts. Trilineage dysplasia was present in 8/28 cases. Median patient survival was 3 months. We conclude that trisomy 13 is particularly associated with acute myeloid leukaemia with minimal differentiation (AML MO), often has distinctive morphological features, and has a poor prognosis.

General Report on the European Union Concerted Action Workshop on 11q23, London, UK, May 1997.

Seventeen cytogenetic laboratories in eight European countries contributed karyotypic, hematological, clinical and follow-up data from 550 patients with an acquired abnormality of 11q23. The patients had acute lymphoblastic leukemia (254), acute myeloid leukemia (250), unspecified, undifferentiated, biphenotypic acute leukemia or myeloproliferative disorder (18 cases together), or myelodysplastic syndrome (MDS) (28). The patients were classified by cytogenetic subgroup as t(4;11) (183 cases), t(6;11) (30) cases), t(9;11) (125 cases), t(10;11) (20 cases), t(11;19) (53 cases), 'other' abnormalities of 11q23 (82 cases) and del(11)(q23) (57 cases). Manuscripts were prepared on each cytogenetic subgroup, on MDS, on secondary hematological malignancies (40 cases) and on 11q23-translocation derivatives. For each subgroup the following aspects were investigated: associated clinical features, additional karyotypic change, distribution between hematological subtypes and between different age groups, prognosis at different age groups, and the impact of bone marrow transplantation on survival. The Workshop confirmed some previous findings from smaller studies, challenged others, identified new chromosomal partners and threw new light on less well documented aspects of 11q23 malignancies. The large number of cases investigated in a coordinated manner gives authoritative support to the findings. The Workshop thus demonstrates the value of collaborative European studies in the cytogenetics of malignancy.

Hematologic malignancies with t(4;11)(q21;q23)--a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants.

A total of 183 hematologic malignancies with t(4;11)(q21;q23), including five variant translocations, were collected by the Workshop. Clinical, morphologic and immunophenotypic features were compiled, and karyotypes with variant t(4;11) or secondary chromosomal aberrations were reviewed. All cases were acute leukemias (AL): 173 acute lymphoblastic leukemias (ALL), six acute myeloid leukemias (AML), three unclassifiable AL, and one biphenotypic AL. Ten patients had treatment-associated AL. Females were overrepresented (104 vs 79) and the age distribution was clearly nonrandom; 34% of the cases occurred in infants below the age of 12 months. The remaining AL were evenly distributed among the other age groups, with the oldest patient being 79 years old. An increased white blood cell count (WBC) was reported in more than 90% of the cases, with hyperleukocytosis (> or =100 x 10(9)/l) in 64%. Additional chromosomal changes were detected in 55 (30%) cases, most often gain of the X chromosome, i(7)(q10), and trisomy 8, with frequent breakpoints in 1p36, 1q21, 7q10, 11p15, 12p13, 17p11, and 17p10. All recurrent secondary changes resulted in genomic imbalances, in particular gains of 1q, 7q, 8, and X and losses of 7p and 17p. Event-free and overall survival (EFS and OS) could be ascertained in 170 and 171 patients, respectively. Kaplan-Meier estimates of EFS and OS showed no differences with regard to gender, WBC, or presence of secondary chromosomal abnormalities, and there was no increase of EFS or OS among the 55 cases that had undergone bone marrow transplantation. However, age had an important prognostic impact, with significantly (P < 0.0001) longer EFS and OS in children 2-9 years old than among infants and younger children, patients aged between 10 and 39 years and older adults.

Hematological malignancies with t(9;11)(p21-22;q23)--a laboratory and clinical study of 125 cases. European 11q23 Workshop participants.

This paper reports clinical and cytogenetic data from 125 cases with t(9;11)(p21-22;q32) which were accepted for a European Union Concerted Action Workshop on 11q23. This chromosome abnormality is known to occur predominantly in acute myeloid leukemia (AML) FAB type M5a and less often in AML M4; in this series it was also found to occur, uncommonly, in other AML FAB types, in childhood acute lymphoblastic leukemia (ALL) (nine cases), in relatively young patients with myelodysplastic syndrome (MDS) (five cases), acute biphenotypic leukemia (two cases), and acute undifferentiated leukemia (one case). All age groups were represented but 50% of the patients were aged less than 15 years. The t(9;11) was the sole abnormality in 57 cases with AML; trisomy 8 was the most common additional abnormality (23 cases, including seven with further abnormalities), and 28 cases had other additional abnormalities. Among the t(9;11)+ve patients with AML, the white cell count (WBC) and age group were significant predictors of event-free survival; central nervous system (CNS) involvement or karyotype class (sole, with trisomy 8, or with other), also contributed to prognosis although our data could not show these to be independent factors. The best outcome was for patients aged 1-9 years, with low WBC, and with absence of CNS disease or presence of trisomy 8. For patients aged less than 15 years, the event-free survival for ALL patients was not significantly worse than that of AML patients.

The t(6;11)(q27;q23) translocation in acute leukemia: a laboratory and clinical study of 30 cases. EU Concerted Action 11q23 Workshop participants.

Thirty patients representing 5.5% of those collected by the 11q23 workshop had a t(6;11)(q27;q23). They included 27cases of acute myeloid leukemia (AML) (M1, three cases; M2, two cases; M4, nine cases; M4/M5, one case; M5, 12 cases) of age range 3-72 years and three cases of acute lymphoblastic leukemia (ALL) (B-lineage ALL, two cases; T-ALL, one case) of age range 0.5-13 years. In 20 cases the t(6;11) was the sole abnormality. In 10 cases the recurrent additional abnormalities were extra copies of chromosomes 8, 19, 21, or the der(6). Translocation t(6;11) was identified by cytogenetics alone in 13 cases. In three cases it was confirmed by fluorescence in situ hybridization (FISH) using whole chromosome paints (wcps) 6 and 11. In a further 14 cases involvement of MLL was demonstrated by FISH, by reverse transcriptase polymerase chain reaction (RT-PCR), by Southern blotting (SB) or by a combination of these methods. One case had a direct insertion of 11 into 6-dir ins(6;11)(q27;q13q23). Molecular investigations showed that one case had a 3' deletion of MLL. The median overall survival for the patients was 12 months, indicating a poor prognosis for patients with a t(6;11) translocation.

The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants.

The clinical, haematological and cytogenetic data for 20 patients with an acquired abnormality of 11q23 and 10p have been reviewed at this workshop. Patients predominantly presented with de novo AML M5a and the most common cytogenetic finding was an inversion of part of the long arm of chromosome 11 followed by a translocation between 11q and 10p. Band p12 represented the most common breakpoint on chromosome 10. The t(10;11) subgroup defined a subset of younger 11q23 patients, the majority of whom achieve a first complete remission despite the differing treatment regimens.

The translocations, t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients. European 11q23 Workshop participants.

The EU Concerted Action Workshop on 11q23 Abnormalities in Hematological Malignancies collected 550 patients with abnormalities involving 11q23. Of these, 53 patients had a translocation involving chromosome 11, breakpoint q23, and chromosome 19, breakpoint p13. Karyogram review enabled each patient to be further defined as t(11;19)(q23;p13.1) (21 patients) or t(11;19)(q23;p13.3) (32 patients). There was a marked difference between the type of banding and the translocation identified: t(11;19)(q23;p13.1) was detected predominantly by R-banding, whereas t(11;19)(q23;p13.3) was detected almost solely by G-banding. Additional change was extremely rare in patients with t(11;19)(q23;p13.1) but occurred in nearly half of the patients with t(11;19)(q23;p13.3). Patients with t(11;19)(q23;p13.1) all had leukemia of a myeloid lineage, mostly acute myeloid leukemia (AML), and were predominantly adult. In contrast patients with t(11;19)(q23;p13.3) had malignancies of both myeloid and lymphoid lineage and were mainly infants less than 1 year old. The survival of both groups of patients was generally poor, over 50% of t(11;19)(q23;p13.1) patients died within 2 years of diagnosis and the median survival of acute lymphoblastic leukemia (ALL) patients with t(11;19)(q23;p13.3) was 17.6 months.