Other subtypes have been identified in B-lineage ALL. The DUX4- and ERG- rearrangement,
identified in about 7% of ALL cases, leads to the formation of an ERG isoform, which induces
leukemic transformation; this lesion is generally associated with a favorable outcome. MEF2D
rearrangements (detected in 3-4% of cases) may be particularly susceptible to histone deacetylase
inhibitors. Finally, ZNF384 deregulation, which can rearrange with several partners (EP300, CREBBP,
TAF15, SYNRG, EWSR1, TCF3 and ARID1B) is detected in 6-7% of cases and often displays a
B/myeloid mixed-phenotype and have an intermediate prognosis.
Lastly, genome-wide sequencing have identified novel mutations and rearrangements; the most
frequent involve the RAS pathway (N/K RAS, FLT3, PTPN11, NF1 and BRAF mutations), can be
detected in more than 40% of cases, prevail in the hyperdiploid and MLL-rearranged cases and tend
to increase at relapse More rare mutations affect the JAK/STAT pathway, i.e. JAK1/2, JAK3 (in T-ALL),
IL7R, rarely CRLF2 mutations, SH2B3 and IL2RB. RAS and JAK/STAT pathway mutations are detected
in both B- and T-lineage ALL.
In T-ALL, NOTCH1/FWB7 lesions represent the most frequent event (about 60% of cases). JAK/STAT
and RAS pathway mutations can also be detected, with a variable frequency (10-30% of cases).
Overexpression of HOX11L2 and ERG, lack of NOTCH1 and FBWX7 mutations, and presence of RAS or
PTEN abnormalities was found to negatively affect prognosis.
Other genetic alterations unrestricted to cell lineage and may impart an adverse outlook are
mutations/alterations of TP53, JAK/STAT, BCL-2, MYC and others. These recent insights point out the
importance of a thorough genetic analysis to improve risk classification, suggesting the use of
combined gene/CNA panels rather than the acquisition of data on single genetic lesions only
SCIENTIFIC
PROGRAMME
RARE SUBSETS OF
ACUTE LEUKAEMIA
TRACKING LEUKAEMIC
STEM CELLS (LSCs)
ROUTINE DIAGNOSIS
GENE EXPRESSION
AND MUTATIONAL
PROFILING
DEBATE 1 – ALL
PATIENTS WITH
INTERMEDIATE-RISK
AML MUST BE
TRANSPLANTED
INTERACTIVE
CASES 1 – MUTATION-BASED
THERAPY
OFF-LABEL
ROUNDTABLE –
SHOULD WE REALLY
USE NEW TARGETED
INHIBITORS AS SINGLE
AGENTS ?
ADDITION OF A 3RD
AGENT TO FRONTLINE
7+3
ROUNDTABLE –
CURATIVE OPTIONS
FOR OLDER AML
INTERACTIVE CASES 2
DEBATE 2 - BEST
TREATMENT FOR
NPM1-MUTATED AML IN
THE NEXT FUTURE ?
ALLOGENEIC
HAEMATOPOIETIC
STEM CELL
TRANSPLANTATION
(HSCT)
IMMUNOTHERAPY FOR
ACUTE LEUKAEMIA
DEBATE 3 - T-ALL:
WHERE ARE WE GOING
NOW?
SELECTED ABSTRACTS
AND CLINICAL
CASES FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
DISCLOSURES