The gene which causes X-linked agammaglobulinemia, btk, has recently been identified as a cytoplasmic tyrosine kinase expressed almost exclusively in B cells, and at all stages of B-cell differentiation. To assess the possibility of involvement of this gene in childhood B-cell malignancies, cells from 23 pediatric patients with B-cell acute lymphoblastic leukemia were examined for expression and alteration of the Btk protein and also for mutations in the btk gene. Btk proteins, similar in both molecular weight and quantity to those seen in unaffected individuals, were detected in whole cell lysates from the blasts of 12/12 patients indicating that no abnormal protein was present. cDNAs from the leukemic blasts of all 23 patients were screened with specific primers covering the coding region of the btk cDNA for mutations using single strand conformation polymorphism (SSCP) analysis. No mutations were found but a nucleotide polymorphism was identified in 4/23 patients at the 3' end of btk. Although the sample size in this study was relatively small, these data suggest that btk does not appear to play a critical role in childhood B-cell leukemias.

HROMOSOME BAND llq23 is the common break- C point region for a number of different reciprocal translocations associated with acute leukemia, including chromosome partners 4q21, 19~13, 6q27, and 9p21. Other chromosomal regions have also been reported, but at a much lower incidence.' These translocations are amongst the most common leukemia-associated chromosome aberra- tions, particularly in infant leukemia where the incidence may be as high as 70%2; altogether they constitute approxi- mately 2% of the total cases of acute lymphoblastic leuke- mia (ALL).3 The clinical features of the infant leukemias associated with the different translocations are broadly Patients usually present with a high white blood cell (WBC) count and there is a female sex bias. Phenotypically, the blast cells are progenitors of B-cell lineage, although some cases coexpress myeloid antigens in addition to lymphoid antigens. The initial response to chemotherapy can be rapid; however, an early relapse (less than 6 months remission) resistant to further treatment is common. How- ever, there are important clinical distinctions that have been noted between the different translocations. The t( 11; 19), t(9;ll), and t(11;17) may be seen in acute myeloid leukemias (AMLs), often with a monocytic component; this is in contrast to the t(4;11), which is only rarely observed in AML.2 The t(6;ll) has only been reported in AML.

Paediatric cochlear implantation 671 implants in Nottingham over a three year period, funding currently allowing 10 implants per year.With increasing experience we haVe extended our initial criteria where implants were only given to children with an acquired hearing loss to include now those with a congenital loss.Initial audiometric criteria have similarly been relaxed, as already noted.Of the 20 children who have so far undergone surgery, 15 of whom were deaf due to meningitis, one operation was unsuccessful due to extensive osteoneogenesis and one child has been explanted.This latter followed development of pain on stimulation and resultant failure to use the implant.No major surgical complications have been experienced and the hearing results may be summarised in table 2. SummaryCochlear implantation may now be considered as a method of managing children with profound sensory hearing loss who do not benefit from conventional amplification.It involves a team approach with integration of many skilled individuals, as well as the child and his or her parents and family.

We have analyzed a series of nine infant leukemias that carry a t(11;19)(q23;p13). They had the morphologic features of acute lymphoblastic leukemia (ALL) and expressed markers typical of B-cell progenitor ALL or pre-B ALL; one coexpressed myeloid markers in addition to lymphoid markers (biphenotypic). Two probes (P/S4 and 98.40) subcloned from a yeast artificial chromosome (YAC) known to span the breakpoint in the t(4;11) were used to investigate DNA isolated from the leukemic cells of these patients. A total of approximately 15 kb of genomic DNA in the vicinity of the probes was examined by conventional Southern blot analysis using a series of restriction enzymes. In eight of the nine cases, the breakpoint could be mapped to an approximately 10-kb BamHI fragment disclosed by hybridization to the P/S4 probe.

Seven new cases are described of near haploid acute lymphoblastic leukemia (ALL) and the findings reviewed together with updated complete remission duration and survival data for the 21 cases already published. The patients were four males and three females, with an age range 2-19 years; all had an immunophenotype consistent with common ALL. The poor prognostic outlook for patients with near haploid ALL is confirmed by the median remission duration of 14 months for these patients, which is comparable to that for the previously published cases. The pattern of chromosome loss was marked particularly by the presence of two copies of chromosomes 10, 14, 18, 21 and both sex chromosomes. Populations of hyperdiploid cells with double the near haploid number were observed in six of the patients, one of whom demonstrated further clonal evolution, and it is proposed that some cases classified as hyperdiploid ALL with greater than 50 chromosomes may also have arisen from a near haploid stem line.

Seven new cases are described of near haploid acute lymphoblastic leukemia (ALL) and the findings reviewed together with updated complete remission duration and survival data for the 21 cases already published. The patients were four males and three females, with an age range 2-19 years; all had an immunophenotype consistent with common ALL. The poor prognostic outlook for patients with near haploid ALL is confirmed by the median remission duration of 14 months for these patients, which is comparable to that for the previously published cases. The pattern of chromosome loss was marked particularly by the presence of two copies of chromosomes 10, 14, 18, 21 and both sex chromosomes. Populations of hyperdiploid cells with double the near haploid number were observed in six of the patients, one of whom demonstrated further clonal evolution, and it is proposed that some cases classified as hyperdiploid ALL with > 50 chromosomes may also have arisen from a near haploid stem line.

We describe four cases of childhood acute lymphoblastic leukemia with monosomy 20 as the sole cytogenetic abnormality. These cases represent 3.4% of cytogenetically abnormal childhood ALL studied in our institute at diagnosis. The patients presented at similar age, ranging from 31 to 36 months. All four patients remain in first remission with survival time being at least 20 months from the time of diagnosis.

SummarySeven cases of infant acute lymphoblastic leukaemia with t(11:19) (q23;p13) are described. They are characterized by a high white cell count, organomegaly, early central nervous system (CNS) disease, and a poor prognosis. Blasts are usually of an immature early B‐cell lineage although monocytoid features are present in some cases. The characteristics of infant acute leukaemia with t(11;19) are very similar to those found with t(4;11), and the presence of t(11;19) may indicate the same poor prognosis.

Three families are presented in which an infant with null acute lymphoblastic leukemia had a karyotype rearrangement involving a break at 1 lq23. Peripheral blood was obtained, where possible, from both parents and from the child during periods of remission. The blood was stimulated with phytohemagglutinin and cultured under conditions that enhance expression of heritable folate-sensitive fragile sites. In all individuals studied very low levels of fra(l l)(q23.3) were observed. These levels were far below those recorded for expression of the heritable folate-sensitive site fra(l l)(q23.3) but are comparable with expression of the common fragile site fra(l l)(q23.3) under these conditions.