Acute lymphoblastic leukemia in infants represents an aggressive malignancy associated with a high incidence (approx. 80%) of translocations involving the Mixed Lineage Leukemia (MLL) gene. Attempts to mimic Mixed Lineage Leukemia fusion driven leukemogenesis in mice raised the question whether these fusion proteins require secondary hits. RAS mutations are suggested as candidates. Earlier resu...

Conversions of leukemic cell lineage (lymphoid or myeloid) have been reported only rarely. Our review of the cytochemical and immunophenotypic features of 89 cases of childhood leukemia in marrow relapse indicated lineage switch (lymphoid to myeloid or the reverse) in six patients (6.7%). Five patients with acute lymphoblastic leukemia (ALL) at diagnosis had converted to acute nonlymphoblastic ...

Background: Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer leading to cancer-related death in children. Most infants with ALL harbor recurring structural chromosomal rearrangements that are important initiating events in leukemogenesis but are insufficient to explain the biology and heterogeneity of the disease. Mixed-lineage leukemia-rearrangement (MLL-rearrange...

Human cancers display substantial intratumoral genetic heterogeneity, which facilitates tumor survival under changing microenvironmental conditions. Tumor substructure and its effect on disease progression and relapse are incompletely understood. In the present study, a high-throughput method that uses neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees w...

BACKGROUND Mature T/ NK-cell neoplasms are a rare group of disorders and their presentation as leukemia is even rarer. Most of the previous studies have focused on mature B-cell lineage leukemias and there is a paucity of data on mature T/NK-cell lineage leukemias. We, therefore, planned this study to analyze their spectrum, frequency, morphology and immunophenotypic features. SUBJECTS AND ME...

Chromosome rearrangements involving the mixed-lineage leukemia gene (MLL) create MLL-fusion proteins, which could drive both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The lineage decision of MLL-fusion leukemia is influenced by the fusion partner and microenvironment. To investigate the interplay of fusion proteins and microenvironment in lineage choice, we transplant...

Faithful modeling of mixed-lineage leukemia in murine cells has been difficult to achieve. We show that expression of MLL-AF9 in human CD34+ cells induces acute myeloid, lymphoid, or mixed-lineage leukemia in immunodeficient mice. Some leukemia stem cells (LSC) were multipotent and could be lineage directed by altering either the growth factors or the recipient strain of mouse, highlighting the...

The use of CAR-T cells will completely change the treatment many hematological diseases, including relapsed pediatric B-lineage acute lymphoblastic leukemia. This article is part Brazilian Society Bone Marrow Transplantation (SBTMO)’s “Technical manual cellular therapy” to guide physicians select patients and indicate in with Other aspects cell therapy management important toxicities are includ...

Early T precursor acute lymphoblastic leukemia (ETP ALL) is rare and has a characteristic phenotype. Mixed phenotype (MPAL), as per World Health Organization, needs to have two different lineages. On cytochemistry, myeloid lineage designated by more than 3% blast cells positivity for cytochemical myeloperoxidase (MPO). Flow cytometric analysis of MPO an arbitrary cutoff 10% been described in th...