Bimodal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia treatment

Jung, Rudolf; Jacobs, U; Krumbholz, Manuela; Langer, Thorsten; Keller, Thomas; Lorenzo, Paola De; Valsecchi, Maria Grazia; Velden, Vincent H.J. van der; Moericke, Anja; Stanulla, Martin; Teigler‐Schlegel, Andrea; Panzer‐Gruemayer, Eva Renate; Dongen, Jacques J. M. van; Schrappe, Martin; Boer, Monique L. den; Pieters, Rob; Rascher, Wolfgang; Metzler, Markus

doi:10.1038/leu.2010.14

Cited by 12 publications

(5 citation statements)

References 12 publications

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“…The multiple breakpoint positions within MLL have an age-dependent distribution, potentially accounting for the distinct biologic behavior of AL in infants compared with children and adults, despite phenotypically and cytogenetically similar disease. 17 11q23 abnormalities have been described in AML evolving from MDS, therapy-related AML, and in several subtypes included in the French-American-British classification. 3,18 The prominent adult-onset age pattern we observed in AML with 11q23 abnormalities, as was similarly seen with therapy-related myeloid neoplasms, may reflect the higher incidence of therapy-related neoplasms and MDS among adults than children.…”

Section: Discussionmentioning

confidence: 99%

Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007

Dores

Devesa

Curtis

et al. 2012

Blood

547

411

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Section: Discussionmentioning

confidence: 99%

Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007

Dores

Devesa

Curtis

et al. 2012

Blood

547

411

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“…While the epidemiology of de novo ( ie., not treatment-related) infant leukemias in the US has not yet found consistent culprits [82, 83], the strong epidemiologic associations with specific clinical therapies in iatrogenic leukemias continues to focus interest on topoisomerases in the causes of infant ALLs. Efforts at examination of MLL breakpoints at the molecular scale have identified a translocation hotspot in therapy-related leukemias [73, 74]; interestingly about half of infant breakpoints have the same molecular phenotype as therapy-related breakpoints suggesting that diverse mechanisms of formation (more than simply topoisomerase II inhibition) may play a role in infants [84-86]. …”

Section: Infant Leukemias and Mll Translocationmentioning

confidence: 99%

Perspectives on the causes of childhood leukemia

Wiemels

2012

Chemico-Biological Interactions

220

155

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Acute leukemia is the most common cancer in children but the causes of the disease in the majority of cases are not known. About 80% are precursor-B cell in origin (CD19+, CD10+), and this immunophenotype has increased in incidence over the past several decades in the Western world. Part of this increase may be due to the introduction of new chemical exposures into the child's environment including parental smoking, pesticides, traffic fumes, paint and household chemicals. However, much of the increase in leukemia rates is likely linked to altered patterns of infection during early childhood development, mirroring causal pathways responsible for a similarly increased incidence of other childhood-diagnosed immune-related illnesses including allergy, asthma, and type 1 diabetes. Factors linked to childhood leukemia that are likely surrogates for immune stimulation include exposure to childcare settings, parity status and birth order, vaccination history, and population mixing. In case-control studies, acute lymphoblastic leukemia (ALL) is consistently inversely associated with greater exposure to infections, via daycare and later birth order. New evidence suggests also that children who contract leukemia may harbor a congenital defect in immune responder status, as indicated by lower levels of the immunosuppressive cytokine IL-10 at birth in children who grow up to contract leukemia, as well as higher need for clinical care for infections within the first year of life despite having lower levels of exposure to infections. One manifestation of this phenomenon may be leukemia clusters which tend to appear as a leukemia “outbreak” among populations with low herd immunity to a new infection. Critical answers to the etiology of childhood leukemia will require incorporating new tools into traditional epidemiologic approaches – including the classification of leukemia at a molecular scale, better exposure assessments at all points in a child's life, a comprehensive understanding of genetic risk factors, and an appraisal of the interplay between infectious exposures and the status of immune response in individuals.

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“…However, rearrangements involving the MLL gene (also known as KMT2A) at chromosome band 11q23 are the best-known hallmark of infantile leukaemia. [ 7 ] Infants with wild-type MLL genes such as our patient have been observed to present after the age of 6 months with more favourable WBC counts and more mature immunophenotypes, as well as a good response to 7-day prednisone monotherapy. [ 8 ] Among infants with wild-type MLL ALL, low levels of MEIS1 expression have been proven to have a superior clinical outcome with a 5-year disease-free survival (DFS) of 87.5 compared to a high MEIS1 expression DFS of 50.0 and 5-year overall survival (OS) of 100.0 and 71.4 for low and high MEIS1 expression, respectively.…”

Section: Discussionmentioning

confidence: 94%

Infantile T-cell Acute Lymphoblastic Leukemia: a Case Report

Baig

Muhammad

Shaikh

2021

J Cancer Allied Spec

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Introduction: Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, with a male predominance. Pediatric acute lymphoblastic leukemia is usually of B-cell lineage; T-cell leukemia is uncommon and extremely rare under one year of age. Mixed-lineage leukemia gene rearrangement is the best-known hallmark of infantile leukemia and is a poor prognostic indicator. While multi-agent high dose chemotherapy remains the first line of treatment for pediatric T-ALL, there are numerous side effects of these regimens, and most patients undergo relapse. Due to the rarity of the disease, treatment protocols for infantile T-ALL have not been established to date. Clinical description: We present a case of a 7-month-old Pakistani male that presented with fever and cough and was subsequently diagnosed with T cell acute lymphoblastic leukemia. T-ALL was diagnosed on flow cytometry. Due to poor prognosis, the patient was assigned palliative care. Practical implications: Management of infantile leukemia has yet to be studied in-depth. With a lack of clear treatment guidelines, the approach towards these patients remains challenging. Further research and clinical trials in this area of study are paramount to improving clinical outcomes for these young patients.

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Bimodal distribution of genomic MLL breakpoints in infant acute lymphoblastic leukemia treatment

Cited by 12 publications

References 12 publications

Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007

Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007

Perspectives on the causes of childhood leukemia

Infantile T-cell Acute Lymphoblastic Leukemia: a Case Report

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