Possible implications for choice of MRD method, timing of MRD monitoring, and guidance of therapy are discussed in general and in some detail for certain types of leukemia with specific molecular markers to monitor, including core binding factor (CBF)-leukemias and NPM1-mutated leukemias.
The apparent nonrandom contribution of the paternally-derived chromosome 9 and the maternally-derived chromosome 22 to the leukemia-specific translocation t(9;22)(q34;q11) obtained by cytogenetic analysis suggested that the two genes affected by this rearrangement, namely ABL and BCR, are imprinted.
To determine whether T-cell acute lymphoblastic leukemia (T-ALL) patient samples possess p53 mutations, we screened peripheral blood-and bone marrow-derived leukemia samples, taken at diagnosis and at relapse, for p53 mutations.
The role of cytidine deaminase and GATA1 mutations in the increased cytosine arabinoside sensitivity of Down syndrome myeloblasts and leukemia cell lines.
Taken together, concomitant blockade of FLT3 and MEK signaling represents a promising treatment strategy for individuals with leukemia who possess activating mutations of FLT3.
This makes an interesting contrast to the case of familial and sporadic leukemias mediated by RUNX1 mutations, in which mutants acting in a dominant negative manner have been suggested to confer a higher propensity to develop leukemia.
The AML1 ( acute myeloid leukemia 1) gene, a necessary prerequisite of embryonic hematopoiesis and a critical regulator of normal hematopoietic development, is one of the most frequently mutated genes in human leukemia, involving over 50 chromosome translocations and over 20 partner genes.
In addition to DNA binding activity, it was critical that specific CpG residues in the Hoxa9 locus were protected from methylation for leukemia development.
There is an urgent need for the development of less toxic, more selective and targeted therapies for infants with leukemia characterized by translocation of the mixed lineage leukemia (MLL) gene.
This breakthrough revolutionized our knowledge related to leukemia biology and contemporary studies revealed that chromosomal translocation resulted in the fusion between the 5' segment of BCR gene and 3' segment of the ABL gene to form BCR/ABL fusion gene.
This view is challenged by a recent observation in a case of leukemia with a complex translocation that results in MLL being fused in-frame to two different partner genes.
Potent graft-versus-leukemia effect after reduced-intensity allogeneic SCT for intermediate-risk AML with FLT3-ITD or wild-type NPM1 and CEBPA without FLT3-ITD.
Additionally, the ETV6-RUNX1 fusion was found to encode putative neoepitopes in a high proportion (69.6%) of the pediatric leukemia harboring this fusion.
We compared the frequency of FLT3-length mutations (FLT3-LM), FLT3-TKD, MLL-partial tandem duplications (MLL-PTD), NRAS, and KITD816 in 381 patients with MDS refractory anemia with excess blasts [RAEB] n=49; with ringed sideroblasts [RARS] n=310; chronic monomyelocytic leukemia [CMML] n=22) and in 4130 patients with AML (de novo: n=3139; secondary AML [s-AML] following MDS: n=397; therapy-related [t-AML]: n=233; relapsed: n=361).
Among the patients with myelofibrosis, those with ASXL1 lesions were not distinguished from their wild-type counterparts with regard to JAK2V617F status, exposure to chemotherapy or evolution to leukemia.
Future studies should focus on clarifying how NPM mutants promote leukemia, integrating NPMc+ AML in the upcoming World Health Organization leukemia classification, and eventually developing specific antileukemic drugs.
These results illustrate a unique paradigm of transcription factor deregulation in leukemia in which DUX4 deregulation results in loss of function of ERG, either by deletion or induced expression of an isoform that is a dominant-negative inhibitor of wild-type ERG function.