Disease relevance of Leukemia, Lymphocytic, Acute, L1

• CONCLUSION: These results indicate that splicing-derived IL-10 isoforms may modulate IL-10-mediated biologic effects and therapeutic efficacy in lymphatic disease, and expression of IL-10delta3 is a positive prognostic feature in relapsed childhood ALL [1].
• In this series of unselected patients, LOH of ETV6 markers was found in 23% of cases (6% of T-ALL and 26% of B lineage ALL) confirming that chromosome 12p12-13 deletions represent a major genetic alteration in childhood ALL, frequently missed by cytogenetic analysis [2].
• Influence of two different Escherichia coli asparaginase preparations on fibrinolytic proteins in childhood ALL [3].
• FLT3 is expressed and activated in many human leukemias, including a significant percentage of pediatric AML and infant and childhood ALL, especially in the setting of MLL gene rearrangement [4].
• West syndrome accounts for about 2% of all childhood epilepsy [5].

High impact information on Leukemia, Lymphocytic, Acute, L1

• Mutations in one gene, connexin 26 (CX26GJB2), are responsible for most cases of recessive non-syndromic deafness, accounting for 30-40% of all childhood genetic deafness in some populations (eg, white people of western European descent) [6].
• Whatever the cause, in childhood ALL variable formation of intracellular mercaptopurine metabolites seems to be clinically important [7].
• These results indicate that genetically determined TPMT activity may be a substantial regulator of the cytotoxic effect of 6-MP, an effect which in turn could be important in influencing the outcome of therapy for childhood ALL [8].
• The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype [9].
• In conclusion, our data support the hypothesis that the leukemia in TEL/AML1-positive childhood ALL originates in a CD19+ lymphoid progenitor [10].

Chemical compound and disease context of Leukemia, Lymphocytic, Acute, L1

• CONCLUSION: These results clearly demonstrate a therapeutic systemic effect of low doses of IT MTX in childhood ALL, and response to prephase therapy should not be considered as an in vivo test for cortico-sensitivity only [11].
• Improving outcome through two decades in childhood ALL in the Nordic countries: the impact of high-dose methotrexate in the reduction of CNS irradiation. Nordic Society of Pediatric Haematology and Oncology (NOPHO) [12].
• We conclude that high VCP expression is associated with poor prednisone response in childhood ALL patients.Leukemia (2006) 20, 820-826. doi:10.1038/sj.leu.2404162; published online 16 March 2006 [13].
• In conclusion, resistance to DNR in childhood ALL can not be explained by decreased levels of Topo II alpha gene expression, but additional Topo II activity studies in fresh leukemia samples may need further exploration [14].
• In conclusion, PNA positivity, especially frequent in T cell ALL, is a marker for a subgroup of childhood ALL patients who are very likely to respond well to systemic PRD 'monotherapy'. In addition, PNA positivity is a favorable prognostic factor in T cell ALL [15].

Biological context of Leukemia, Lymphocytic, Acute, L1

• Therefore, we studied 45 cases of childhood ALL with abnormalities of chromosome 11q23 for rearrangement of the MLL gene to determine if this feature confers a uniformly poor prognosis [16].
• These studies show that LOH at the TEL locus is a frequent finding in childhood ALL [17].
• In conclusion, increased BCL-2 expression in childhood ALL appears to enhance the ability of lymphoblasts to survive without essential trophic factors, and is inversely related to the presence of chromosomal translocations [18].
• Frameshift mutations were found at trinucleotide repeats within a coding exon of the E2F4 gene in 2 of 10 (20%) ATL samples and 1 of 9 (11%) childhood ALL samples [19].
• Molecular quantification of response to therapy and remission status in TEL-AML1-positive childhood ALL by real-time reverse transcription polymerase chain reaction [20].

Anatomical context of Leukemia, Lymphocytic, Acute, L1

• To address this assumption and to investigate the prognostic significance of TEL-AML1 expression in relapsed childhood ALL, bone marrow samples of 146 children were analyzed by reverse-transcriptase (RT)-polymerase chain reaction (PCR) [21].
• To address the significance of beta-tubulin and MAP4 alterations in childhood ALL, two CCRF-CEM-derived Vinca alkaloid resistant cell lines, VCR R (vincristine) and VLB100 (vinblastine), were examined [22].

Gene context of Leukemia, Lymphocytic, Acute, L1

• We therefore conclude that the presence of a homozygous p16 deletion may well be an important risk factor for both relapse and death in childhood ALL, and that its prognostic effect is not a consequence of confounding by other factors already known to influence outcome in this disease [23].
• To identify new partner breakpoints for ETV6 and CBFA2, we selected 30 patients with childhood ALL in whose leukemic cells a t(12;21) had been detected by RT-PCR [24].
• Expression of LRP, but not of P-gp and MRP, significantly correlated with DNR resistance in childhood ALL (Rs 0. 33, P = 0.03) [25].
• We recommend the use of the above mentioned fixation methods in order to study the clinical relevance of P-gp, MRP and LRP in childhood ALL [26].
• These findings suggest that GSTP1 variants (alone or combined with other GSTs) represent significant genetic determinants of childhood ALL [27].

Analytical, diagnostic and therapeutic context of Leukemia, Lymphocytic, Acute, L1

• CONCLUSION: We show for the first time that potential alteration in p53 function in childhood ALL is more common (P = .036) in cases of early treatment failure than in children who remain in long-term continuous remission [28].
• Screening of 372 patients who were enrolled in two consecutive Austrian childhood ALL multicenter trials identified 94 (25%) TEL/AML1+ cases [29].
• In contrast to childhood ALL, induction chemotherapy should include another drug (or drugs) in addition to VCR and prednisolone, and one of the anthracycline drugs (ADR or DNR) has been employed most frequently in this context [30].
• Whereas the relationship between the clinical pharmacology, and potentially important pharmacodynamic effects such as asparagine depletion, has been well characterized for therapy with L-asparaginase, similar studies have yet to be performed for the other drugs that form the mainstay of remission induction therapy for childhood ALL [31].
• Using PBPC for allogeneic transplantation in childhood ALL results in faster hematopoietic recovery compared to BM, with a similar incidence of aGVHD, TRM, relapse and disease-free survival [32].

References