Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in infants have in common a high incidence of translocations of the MLL gene at chromosome band 11q23.
Acute lymphoblastic leukemia (ALLs) expressing MLL-AF4, the fusion product of t(4;11)(q21;q23), show marked leucocytosis and extramedullary disease in multiple organs, respond poorly to chemotherapy and have poor prognosis.
Acute lymphoblastic leukemia (ALL) in infants younger than 1 year is a rare but relatively homogeneous disease ( approximately 80% MLL gene rearranged, approximately 70% CD10-negative) when compared with childhood and adult ALL.
Acute lymphoblastic leukemia (ALL) in infants is an aggressive malignancy with a poor clinical outcome, and is characterized by translocations of the Mixed Lineage Leukemia (MLL) gene.
Acute lymphoblastic leukemia (ALL) with mixed lineage leukemia (MLL) gene rearrangements (MLL+ALL) has a dismal prognosis and is characterized by high surface CD44 expression.
MLL gene rearrangements are associated with coexpression of myeloid- and lymphoid-associated antigens on leukemic blasts and a dismal outcome in acute lymphoblastic leukemia (ALL).
MLL-AF9 is the most frequent MLL rearrangement in childhood acute myeloid leukemia (AML) and it may be also found in acute lymphoblastic leukemia (ALL) of patients younger than 1-year-old (infants).
MLL+ALL has a unique gene profile distinguishable from other types of ALL and AML, and should be investigated separately in responses to biological active agents including chemokine inhibitors.
MLL (also known as ALL-I, HTRX, or HRX) gene translocations are among the most common chromosomal abnormalities recognized in both B-lineage acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).
MLL is involved in translocations that result in de novo acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), mixed lineage leukemia, and also in therapy AML (t-AML) and therapy ALL (t-ALL) resulting from treatment with DNA topoisomerase II (topo II) targeting drugs.
After referral to our clinic, tests of the morphology, immunology, cytogenetics, and molecular biology of his bone marrow led to a diagnosis of MLL-AF4 fusion positive B-cell ALL.
Age was not related to cellular drug resistance within the proB ALL group (<1 year, n=32, vs >/=1 year, n=19), nor within the MLL-rearranged ALL (<1 year, n=34, vs >/=1 year, n=8).
ALL related to prior cytotoxic therapy (t-ALL) appears to be a distinct entity when compared to the de novo ALL, with characteristics including older age at the time of onset, female predominance and leukemia genetics enriched with KMT2A (MLL) gene rearrangement and chromosomes 5/7 abnormalities.
Although MLL gene rearrangements are generally associated with a dismal outcome in ALL, two distinct subsets with MLL-ENL fusions have an excellent prognosis.
Although KMT2A rearrangement is the predominant genetic signature in infantile B-ALL, disease course is heterogenous, behaving more aggressively in younger infants.
Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with current therapy, the event-free survival (EFS) of infants with ALL, particularly those with mixed lineage leukemia (MLL) gene rearrangements, is only 30% to 40%.
Among B-cell precursor ALL cases, high white blood cell counts correlated with earlier age at diagnosis (rS=-0.23; P<0.001) being most evident for 11q23/MLL-aberrations, translocation t(12;21)(p13;q22), and high-hyperdiploidy.
Among the three age groups, older patients more often had higher risk ALL due to T-ALL (32%/25%/9%, P<0.001), KMT2A rearrangements (6%/5%/3%, P<0.001) and higher day 29 residual leukemia for B-lineage (P<0.001), but not T-ALL (P=0.53).
Analysis of the outcome among ALL infants with MLL gene rearrangements registered in the Japan Infant Leukemia Study between 1996 and 1999 showed the event-free survival of patients with t(9;11) was not different from that of those with other 11q23 translocations.
At present, all cell strains derived from acute lymphoblastic leukemia (ALL) patients with the long arm of chromosome 11 aberration are accompanied with mixed lineage leukemia (MLL) gene rearrangement.
At the extreme end of the risk spectrum, the t(4;11)/MLL-AF4 and t(9;22)/BCR-ABL almost always confer a dire prognosis in both children and adults with ALL, who warrant high-dose chemotherapy and hematopoietic stem cell rescue to sustain or even induce first remission.
Based on 7969 cases of acute myeloblastic leukemia (AML) and 1252 cases of acute lymphoblastic leukemia (ALL) taken from the literature, band 11q23 and/or the MLL gene was involved in 5.2% of AML and 22% of ALL.