Heterogeneity of the 7q36 breakpoints in the t(7;12) involvingETV6 in infant leukemia

2003 ◽  
Vol 38 (2) ◽  
pp. 191-200 ◽  
Author(s):  
Sabrina Tosi ◽  
Jim Hughes ◽  
Stephen W. Scherer ◽  
Kazuhiko Nakabayashi ◽  
Jochen Harbott ◽  
...  
Keyword(s):  
Infant Leukemia

scholarly journals The efficiency of murine MLL-ENL–driven leukemia initiation changes with age and peaks during neonatal development

2019 ◽  
Vol 3 (15) ◽  
pp. 2388-2399 ◽  
Author(s):  
Theresa Okeyo-Owuor ◽  
Yanan Li ◽  
Riddhi M. Patel ◽  
Wei Yang ◽  
Emily B. Casey ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Transgene Expression ◽  
Target Genes ◽  
Lymphoblastic Leukemia ◽  
Human Infant ◽  
Driver Mutations ◽  
Hematopoietic Progenitors ◽  
Adult Mice ◽  
Almost All ◽  
Infant Leukemia

Abstract MLL rearrangements are translocation mutations that cause both acute lymphoblastic leukemia and acute myeloid leukemia (AML). These translocations can occur as sole clonal driver mutations in infant leukemias, suggesting that fetal or neonatal hematopoietic progenitors may be exquisitely sensitive to transformation by MLL fusion proteins. To test this possibility, we used transgenic mice to induce one translocation product, MLL-ENL, during fetal, neonatal, juvenile and adult stages of life. When MLL-ENL was induced in fetal or neonatal mice, almost all died of AML. In contrast, when MLL-ENL was induced in adult mice, most survived for >1 year despite sustained transgene expression. AML initiation was most efficient when MLL-ENL was induced in neonates, and even transient suppression of MLL-ENL in neonates could prevent AML in most mice. MLL-ENL target genes were induced more efficiently in neonatal progenitors than in adult progenitors, consistent with the distinct AML initiation efficiencies. Interestingly, transplantation stress mitigated the developmental barrier to leukemogenesis. Since fetal/neonatal progenitors were highly competent to initiate MLL-ENL–driven AML, we tested whether Lin28b, a fetal master regulator, could accelerate leukemogenesis. Surprisingly, Lin28b suppressed AML initiation rather than accelerating it. This may explain why MLL rearrangements often occur before birth in human infant leukemia patients, but transformation usually does not occur until after birth, when Lin28b levels decline. Our findings show that the efficiency of MLL-ENL–driven AML initiation changes through the course of pre- and postnatal development, and developmental programs can be manipulated to impede transformation.

scholarly journals MLL gene rearrangements in infant leukemia vary with age at diagnosis and selected demographic factors: A Children's Oncology Group (COG) study

2011 ◽  
Vol 58 (6) ◽  
pp. 836-839 ◽  
Author(s):  
Thien N. Sam ◽  
John H. Kersey ◽  
Amy M. Linabery ◽  
Kimberly J. Johnson ◽  
Nyla A. Heerema ◽  
...  
Keyword(s):  
Demographic Factors ◽  
Age At Diagnosis ◽  
Gene Rearrangements ◽  
Oncology Group ◽  
Mll Gene ◽  
Infant Leukemia

scholarly journals Treatment of infant leukemias: challenge and promise

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 596-600 ◽  
Author(s):  
Patrick Brown
Keyword(s):  
High Frequency ◽  
Clinical Presentation ◽  
State Of The Art ◽  
Poor Response ◽  
Cooperative Groups ◽  
Therapeutic Approaches ◽  
Unique Biology ◽  
Current Therapies ◽  
Epidemiologic Features ◽  
Infant Leukemia

Abstract Leukemia in infants is rare but generates tremendous interest due to its aggressive clinical presentation in a uniquely vulnerable host, its poor response to current therapies, and its unique biology that is increasingly pointing the way toward novel therapeutic approaches. This review highlights the key clinical, pathologic, and epidemiologic features of infant leukemia, including the high frequency of mixed lineage leukemia (MLL) gene rearrangements. The state of the art with regard to current approaches to risk stratified treatment of infant leukemia in the major international cooperative groups is discussed. Finally, exciting recent discoveries elucidating the molecular biology of infant leukemia are reviewed and novel targeted therapeutic strategies, including FLT3 inhibition and modulation of aberrant epigenetic programs, are suggested.

scholarly journals Defining the fetal origin of MLL-AF4 infant leukemia highlights specific fatty acid requirements

Cell Reports ◽  
2021 ◽  
Vol 37 (4) ◽  
pp. 109900
Author(s):  
Vasiliki Symeonidou ◽  
Hélène Jakobczyk ◽  
Salem Bashanfer ◽  
Camille Malouf ◽  
Foteini Fotopoulou ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Specific Fatty Acid ◽  
Fetal Origin ◽  
Infant Leukemia

scholarly journals Infant leukemia and parental infertility or its treatment: a Children's Oncology Group report

2010 ◽  
Vol 25 (6) ◽  
pp. 1561-1568 ◽  
Author(s):  
S. E. Puumala ◽  
L. G. Spector ◽  
M. M. Wall ◽  
L. L. Robison ◽  
N. A. Heerema ◽  
...  
Keyword(s):  
Oncology Group ◽  
Group Report ◽  
Infant Leukemia

406: Birth Weight and the MLL Gene in Infant Leukemia: A Children's Oncology Group Study

2005 ◽  
Vol 161 (Supplement_1) ◽  
pp. S102-S102
Author(s):  
L G Spector ◽  
S M Davies ◽  
L L Robison ◽  
M Roesler ◽  
J A Ross
Keyword(s):  
Birth Weight ◽  
Oncology Group ◽  
Oncology Group Study ◽  
Mll Gene ◽  
Infant Leukemia

scholarly journals Targeting Epigenetic Programs in MLL-Rearranged Leukemias

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 354-360 ◽  
Author(s):  
Kathrin M. Bernt ◽  
Scott A. Armstrong
Keyword(s):  
Hox Genes ◽  
Myelogenous Leukemia ◽  
Wild Type ◽  
Leukemic Transformation ◽  
Acute Leukemias ◽  
Important Mediator ◽  
Acute Myelogenous ◽  
Epigenetic Regulators ◽  
Inappropriate Expression ◽  
Infant Leukemia

Abstract Rearrangements of the Mixed-Lineage Leukemia (MLL) gene are found in > 70% of infant leukemia, ∼ 10% of adult acute myelogenous leukemia (AML), and many cases of secondary acute leukemias. The presence of an MLL rearrangement generally confers a poor prognosis. There are more than 60 known fusion partners of MLL having some correlation with disease phenotype and prognosis. The most common fusion proteins induce the inappropriate expression of homeotic (Hox) genes, which, during normal hematopoiesis, are maintained by wild-type MLL. MLL-rearranged leukemias display remarkable genomic stability, with very few gains or losses of chromosomal regions. This may be explained by recent studies suggesting that MLL-rearranged leukemias are largely driven by epigenetic dysregulation. Several epigenetic regulators that modify DNA or histones have been implicated in MLL-fusion driven leukemogenesis, including DNA methylation, histone acetylation, and histone methylation. The histone methyltransferase DOT1L has emerged as an important mediator of MLL-fusion–mediated leukemic transformation. The clinical development of targeted inhibitors of these epigenetic regulators may therefore hold promise for the treatment of MLL-rearranged leukemia.

Abstract 1175: Inhibition of NAMPT as a novel therapeutic strategy for infant leukemia

2017 ◽  
Author(s):  
Klaartje Somers ◽  
Shiloh Middlemiss ◽  
Asel Biktasova ◽  
Mawar Karsa ◽  
Leanna Cheung ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Infant Leukemia ◽  
Novel Therapeutic

MLL rearrangements in infant leukemia: Is there a higher frequency in females?

1997 ◽  
Vol 21 (8) ◽  
pp. 793-795 ◽  
Author(s):  
Julie A. Ross ◽  
Leslie L. Robison
Keyword(s):  
Infant Leukemia
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