Aug 04, · For the group of acute leukemias that have characteristics of both AML and acute lymphoblastic leukemia (ALL), the acute leukemias of ambiguous lineage, the WHO classification system is summarized in Table 1.[13,14] The criteria for lineage assignment for a diagnosis of mixed phenotype acute leukemia (MPAL) are provided in Table 2.[12,15] Chromosome 21 is the most affected chromosome in childhood acute lymphoblastic leukemia. Many of its numerical and structural abnormalities define diagnostically and clinically important subgroups. To obtain an overview about their types and their approximate genetic subgroup-specific incidence and distribution, we performed cytogenetic, FISH and array analyses in a UpToDate, electronic clinical resource tool for physicians and patients that provides information on Adult Primary Care and Internal Medicine, Allergy and Immunology, Cardiovascular Medicine, Emergency Medicine, Endocrinology and Diabetes, Family Medicine, Gastroenterology and Hepatology, Hematology, Infectious Diseases, Nephrology and Hypertension, Neurology,
Acute lymphoblastic leukemia - Wikipedia
Cancer in children and adolescents is rare, although the overall incidence of childhood cancer, including ALL, has acute lymphoblastic leukemia effect on the developmental process slowly increasing since Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors. The incidence of ALL appears to be highest in Hispanic children 43 cases per 1 million.
Childhood ALL originates in the T and B lymphoblasts in the bone marrow refer to Figure 1. Enlarge Figure 1. Blood cell development. Different blood and immune cell lineages, including T and B lymphocytes, differentiate from a common blood stem cell.
Marrow involvement of acute leukemia as seen by light microscopy is defined as follows:, acute lymphoblastic leukemia effect on the developmental process. In the past, ALL lymphoblasts were classified using the French-American-British FAB criteria as having L1 morphology, L2 morphology, or L3 morphology.
Most cases of ALL that show L3 morphology express surface immunoglobulin Ig and have a MYC gene translocation identical to those seen in Burkitt lymphoma i. Patients with this specific rare form of leukemia mature B-cell or Burkitt leukemia should be treated according to protocols for Burkitt lymphoma.
Few factors associated with an increased risk of ALL have been identified. The primary accepted risk factors for ALL and associated genes when relevant include the following:.
Children with Down syndrome have an increased risk of developing both ALL and AML,[ 2223 ] with a cumulative risk of developing leukemia of approximately 2. A genome-wide association study found that four susceptibility loci associated with B-ALL in the non-Down syndrome population IKZF1CDKN2Aacute lymphoblastic leukemia effect on the developmental process, ARID5Band GATA3 were also associated with susceptibility to ALL in children with Down syndrome, acute lymphoblastic leukemia effect on the developmental process.
Genetic predisposition to ALL can be divided into several broad categories, as follows:. Genetic risk factors for T-ALL share some overlap with the genetic risk factors for B-ALL, but unique risk factors also exist. A genome-wide association study identified a risk allele near USP7 that was associated with an increased risk of developing T-ALL odds ratio, 1.
The risk allele was shown to be associated with reduced USP7 transcription, which acute lymphoblastic leukemia effect on the developmental process consistent with the finding that somatic loss-of-function mutations in USP7 are observed in patients with Acute lymphoblastic leukemia effect on the developmental process. USP7 germline and somatic mutations are generally mutually exclusive and are most commonly observed in T-ALL patients with TAL1 alterations.
Development of ALL is a multistep process in most cases, with more than one genomic alteration required for frank leukemia to develop. In at least some cases of childhood ALL, the initial genomic alteration appears to occur in utero. Evidence also exists that some children who never develop ALL are born with rare blood cells carrying a acute lymphoblastic leukemia effect on the developmental process alteration associated with ALL.
Initial studies focused on the ETV6-RUNX1 translocation and used reverse transcriptase RT —polymerase chain reaction PCR to identify RNA transcripts indicating the presence of the gene acute lymphoblastic leukemia effect on the developmental process. The typical and atypical symptoms and clinical findings of childhood ALL have been published. The evaluation needed to definitively diagnose childhood ALL has been published.
Despite the treatment advances in childhood ALL, numerous important biologic and therapeutic questions remain to be answered before the goal of curing every child with ALL with the least associated toxicity can be achieved.
The systematic investigation of these issues requires large clinical trials, and the opportunity to participate in these acute lymphoblastic leukemia effect on the developmental process is offered to most patients and families. In certain trials in which the cure rate for the patient group is very high, therapy reduction questions may be asked. Much of the progress made in identifying curative therapies for childhood ALL and other childhood cancers has been achieved through investigator-driven discovery and tested in carefully randomized, controlled, multi-institutional clinical trials.
Information about ongoing clinical trials is available from the NCI website. Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients, acute lymphoblastic leukemia effect on the developmental process.
The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available. The revision to the WHO classification of tumors of the hematopoietic and lymphoid tissues lists the following entities for acute lymphoid leukemias:[ 1 ].
For acute leukemias of ambiguous lineage, the group of acute leukemias that have characteristics of both acute myeloid leukemia AML and acute lymphoblastic leukemia ALLthe WHO classification system is summarized in Table 1. Leukemias of mixed phenotype may be seen in various presentations, including the following:.
Biphenotypic cases represent the majority of mixed phenotype leukemias. The genomics of childhood ALL has been extensively investigated, and multiple distinctive subtypes have been defined on the basis of cytogenetic and molecular characterizations, each with its own pattern of clinical and prognostic characteristics. The genomic landscape of B-ALL is typified by a range of genomic alterations that disrupt normal B-cell development and, in some cases, by mutations in genes that provide a proliferation signal e.
Genomic alterations leading to blockage of B-cell development include translocations e. The genomic alterations in B-ALL tend not to occur at random, but rather to cluster within subtypes that can be delineated by biological characteristics such as their gene expression profiles. Cases with recurring chromosomal translocations e.
Activating point mutations in kinase genes are uncommon in high-risk B-ALL. JAK genes are the primary kinases that are found to be mutated. Understanding of the genomics of B-ALL at relapse is less advanced than acute lymphoblastic leukemia effect on the developmental process understanding of ALL genomics at diagnosis.
Childhood ALL is often polyclonal at diagnosis and under the selective influence of therapy, some clones may be extinguished and new clones with distinctive genomic profiles may arise. The PRSP1 mutations observed in relapsed cases induce resistance to thiopurines in leukemia cell lines. CREBBP mutations are also enriched at relapse and appear to be associated with increased resistance to glucocorticoids. A number of recurrent chromosomal abnormalities have been shown to have prognostic significance, especially in B-ALL.
Some chromosomal alterations are associated with more favorable outcomes, such as high hyperdiploidy 51—65 chromosomes and the ETV6-RUNX1 fusion. In recognition of the clinical significance of many of these genomic alterations, the revision of the World Health Organization classification of tumors of the hematopoietic and lymphoid tissues lists the following entities for B-ALL:[ 17 ].
These and other chromosomal and genomic abnormalities for childhood ALL are described below. High hyperdiploidy, defined as 51 to 65 chromosomes per cell or a DNA index greater than 1, acute lymphoblastic leukemia effect on the developmental process. In cases with a normal karyotype or in which standard cytogenetic analysis was unsuccessful, interphase fluorescence in situ hybridization FISH may detect hidden hyperdiploidy.
While the overall outcome of patients with high hyperdiploidy is considered to be favorable, factors such as age, WBC count, specific trisomies, and early response to treatment have been shown to modify its prognostic significance.
Patients with trisomies of chromosomes 4, 10, and 17 triple trisomies have been shown to have a particularly favorable outcome, as demonstrated by both Pediatric Oncology Group POG and Children's Cancer Group analyses of National Cancer Institute NCI standard-risk ALL. Chromosomal translocations may be seen with high hyperdiploidy, and in those cases, patients are more appropriately risk-classified on the basis of the prognostic significance of the translocation.
Certain patients with hyperdiploid ALL may have a hypodiploid clone that has doubled masked hypodiploidy. These patients have an unfavorable outcome, similar to those with hypodiploidy. Genes encoding histone modifiers are also present in a recurring manner in a minority of cases. Analysis of mutation profiles demonstrates that chromosomal gains are early events in the pathogenesis of hyperdiploid ALL. B-ALL cases with fewer than the normal number of chromosomes have been subdivided in various ways, with one report stratifying on the basis of modal chromosome number into the following four groups:[ 28 ].
Most patients with hypodiploidy are in the near-haploid and low-hypodiploid groups, and both of these groups have an elevated risk of treatment failure compared with nonhypodiploid cases. The recurring genomic alterations of near-haploid and low-hypodiploid ALL appear to be distinctive from each other and from other types of ALL.
Reports generally indicate favorable EFS and overall survival OS in children with the ETV6-RUNX1 fusion; however, the prognostic impact of this genetic feature is modified by the following factors:[ 42 - 46 ]. In one study of the treatment of newly diagnosed children with ALL, multivariate analysis of prognostic factors found age and leukocyte count, but not ETV6-RUNX1acute lymphoblastic leukemia effect on the developmental process, to be independent prognostic factors. There is a higher frequency of late relapses in patients with ETV6-RUNX1 fusions compared with other relapsed B-ALL patients.
The Ph chromosome t 9;22 q Enlarge Figure 3. The Philadelphia chromosome is a translocation between the ABL1 oncogene on the long arm of chromosome 9 and the BCR gene on the long arm of chromosome 22resulting in the fusion gene BCR-ABL1. BCR-ABL1 encodes an oncogenic protein with tyrosine kinase activity.
This subtype of ALL is more common in older children with B-ALL and high WBC count, with the incidence of the t 9;22 q Historically, the Ph chromosome t 9;22 q These rearrangements are generally associated with an increased risk of treatment failure. Patients with the t 4;11 q21;q23 are usually infants with high WBC counts; they are more likely than other children with ALL to have central nervous system CNS disease and to have a poor response to initial therapy.
Whole-genome sequencing has determined that cases of infant ALL with KMT2A gene rearrangements have few additional genomic alterations, none of which have clear clinical significance. Of interest, the t 11;19 q23;p The t 1;19 had been associated with inferior outcome in the context of antimetabolite-based therapy,[ 71 ] but the adverse prognostic significance was largely negated by more aggressive multiagent therapies.
Jude Children's Research Hospital SJCRH on which all patients were treated without cranial radiation, patients with the t 1;19 had an overall outcome comparable to children lacking this translocation, with a higher risk of CNS relapse and a lower rate of bone marrow relapse, suggesting that more intensive CNS therapy may be needed for these patients.
ALL with the TCF3-HLF fusion is associated with disseminated intravascular coagulation and hypercalcemia at diagnosis. Outcome is very poor for children with the t 17;19with a literature review noting mortality for 20 of 21 cases reported. The most common rearrangement produces IGH-DUX4 fusions, with ERG-DUX4 fusions also observed.
Cases with MEF2D gene fusions show a distinctive gene expression profile, except for rare cases with MEF2D-CSFR1 that have a Ph-like gene expression profile. The median age at diagnosis for cases of MEF2D -rearranged ALL in studies that included both adult and pediatric patients was 12 to 14 years. Regardless of the fusion partner, ZNF -rearranged ALL cases show a distinctive gene expression profile.
This entity is included in the revision of the WHO classification of tumors of the hematopoietic and lymphoid tissues. The number of cases of IL3-IGH ALL described in the published literature is too small to assess the prognostic significance of the IL3-IGH fusion. Diagnosis of cases of IL3-IGH ALL may be delayed because it can present with hypereosinophilia in the absence of cytopenias and circulating blasts.
Gene expression analysis identified two distinctive ALL acute lymphoblastic leukemia effect on the developmental process with PAX5 genomic alterations, termed PAX5alt and PAX5 p. PAX5 alt. PAX5 p. PAX5 with a p. Pro80Arg mutation shows a gene expression profile distinctive from that of other cases with PAX5 alterations. Outcome for the pediatric patients with PAX5 p. BCR-ABL1 —negative patients with a gene expression profile similar to BCR-ABL1 —positive patients have been referred to as Ph-like, acute lymphoblastic leukemia effect on the developmental process.
Retrospective analyses have indicated that patients with Ph-like ALL have a poor prognosis. In a COG study, Many of the remaining cases of Ph-like ALL have been noted to have a series of translocations with a common theme of involvement of kinases, including ABL1ABL2CSF1RJAK2and PDGFRB.
Acute Lymphoblastic Leukemia - Chemotherapy and Radiotherapy
, time: 2:01
Oct 04, · The Journal of Pediatrics is an international peer-reviewed journal that advances pediatric research and serves as a practical guide for pediatricians who manage health and diagnose and treat disorders in infants, children, and blogger.com Journal publishes original work based on standards of excellence and expert review. The Journal seeks to publish high Acute lymphoblastic leukemia (ALL) is a cancer of the lymphoid line of blood cells characterized by the development of large numbers of immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, easy bleeding or bruising, enlarged lymph nodes, or bone pain. As an acute leukemia, ALL progresses rapidly and is typically fatal within weeks or For acute lymphoblastic leukemia (ALL), the 5-year survival rate has improved significantly since Get information about risk factors, signs, diagnosis, molecular features, survival, risk-based treatment assignment, and induction and postinduction therapy for children and adolescents with newly diagnosed and recurrent ALL
No comments:
Post a Comment