Page 58 - Haematologica Vol. 107 - September 2022

ARTICLE - Genetic abnormalities in older ALL patients
T. Creasey et al.
p.V32G in a patient with P2RY8-CRLF2). Additionally, pre- viously unreported KDM6A mutations were discovered in two BCR-ABL1-positive patients (KDM6A p.Y215H and p.K987Q).
We also investigated whether mutations associated with clonal hematopoiesis of indeterminate potential (CHIP)
(most commonly affecting DNMT3A, TET2 and ASXL1) were present in older adults with ALL.29,30 These are found in 10% of adults over the age of 65 years without hemato- logic diseases, but are associated with an increased risk of subsequently developing myelodysplastic syndrome or acute myeloid leukemia.30 Overall, these were discovered
Table 3. Demographic, clinical and outcome data of all cases with focal LEMD3 or KDM6A deletions.
Gene
Patient ID
Sex (M/F)
Age (years)
Genetic subgroup
WCC (x109/L)
Outcome
LEMD3
25208
M
62
BCR-ABL1
205.4
Alive after 9 years
LEMD3
25130
F
62
IGH-CRLF2
33.6
Died after 1 month
LEMD3
28670
F
61
BCR-ABL1
1.6
Died after 2 months
LEMD3
26660
F
62
BCR-ABL1
18.2
Alive after 7 years
LEMD3
25552
M
61
P2RY8-CRLF2
2.9
Died after 4 months
KDM6A
28011
M
61
B-other
3.5
Died after 16 months
KDM6A
29407
F
60
HoTr
2.9
Died after 5 months
KDM6A
25437
F
64
HoTr
1.4
Died after 14 months
KDM6A
27642
F
72
T-ALL
Not known
Died after 18 months
All patients with KDM6A deletions died within 18 months of diagnosis. ID: identifier; M: male; F: female; WCC: white blood cell count; HoTr: low hypodiploidy/near triploidy; T-ALL: T-cell acute lymphoblastic leukemia
Figure 3. Mutations detected by the 44-gene next-generation sequencing panel in 23 patients. Only patients’ samples with at least one mutation are displayed (n=17). In total, 24 single nucleotide variants, seven frameshift insertions and one frameshift deletion were identified. Two genes had both single nucleotide variants and indels within the same case (“multi-hit”). HoTr: low hypodiploidy/near triploidy; T-ALL: T-cell acute lymphoblastic leukemia; B-other: B-cell precursor acute lymphoblastic leukemia in which no primary chromosomal abnormality was identified.
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