The BCL2-inhibitor venetoclax was highly active below 10 nM in B-cell precursor ALL (BCP-ALL) subsets, including <i>MLL</i><i>-AF4</i> and <i>TCF3-HLF</i> ALL, and in some T-cell ALLs (T-ALLs), predicting in vivo activity as a single agent and in combination with dexamethasone and vincristine.
We observed a high degree of clonal heterogeneity and evolution between diagnosis and relapse in both BCP-ALL and T-ALL, which could have implications for the treatment efficiency.
Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified.
A higher specific hazard of relapse was independently associated with postinduction MRD level ≥10(-4) and unfavorable genetic characteristics (ie, MLL gene rearrangement or focal IKZF1 gene deletion in BCP-ALL and no NOTCH1/FBXW7 mutation and/or N/K-RAS mutation and/or PTEN gene alteration in T-cell ALL).
Five 'hot topics' are presented in which cytogenetics and related techniques have been instrumental in understanding the role of genetics in leukaemogenesis: (i) genetic changes are integral to the biology of T-cell ALL; (ii) intrachromosomal amplification of chromosome 21 is a new recurrent abnormality in precursor-B ALL (BCP-ALL); (iii) the immunoglobulin heavy chain gene (IGH@) is significant in BCP-ALL; (iv) alterations in genes involved in B-cell development and cell cycle control contribute to the pathogenesis of BCP-ALL; (v) age-related cytogenetic profiles define ALL in children and adolescents as distinct biological entities.
The clinical importance of T-ALL lies in its poor responsiveness to therapy that has proved highly effective with standard B-cell precursor ALL (BCP-ALL).