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Letters to the Editor
cific STAT5 activation as a downstream target (Figure 1B). ERK1/2 phosphorylation was also increased (Figure 1C).
In order to study the cell-of-origin of the ETV6-ABL1 fusions, various cell populations from two patients (Patients 1 and 4) were sorted based on immunopheno- type by flow cytometry, including CD34+CD38– (hematopoietic stem cells and early progenitors, HSPC),
CD34+CD38+ (late committed progenitors), monocytes, granulocytes and lymphocytes. FISH studies were per- formed on the sorted cells. ETV6 rearrangements were observed in CD34+CD38–, CD34+CD38+, monocytes, and granulocytes but not in mature lymphocytes (Figure 1F- K), supporting the view that ETV6-ABL1 fusions originate from HSPC.
Table 1. Clinicopathologic features of myeloid neoplasms with ETV6-ABL1 fusions.
PatientID 123456
Age/Sex 34 yrs/M 45 yrs/M 23 yrs/M 55 yrs /F
Splenomegaly Yes Yes Yes No
54 yrs/M
Yes
217
7.8
191
2.0
2.1 >90% Increased, hypolobated
88 yrs/F
No
14.5 11.7
417
2.6
0.6
75% Increased, hy-polobated
WBC (x109/L)
Hb (g/dL)
PLT (x109/L)
Abs Eo(x109/L) at presentation Abs Baso(x109/L) at presentation BM cellularity
Megakaryocytes
27 17.2 374 13.9 11.6 6 236 203 76
1.7 1.7 44.5
0.5 0.2 3.7 Normal* 100% 100%
Unremarkable* Ranging from Unremarkable small to large,
clustering
7.3* 10:1 >10:1
9
12.5 818
9.2
0.2 100% Increased, large, clustering 10:1
M:E ratio
Eo(%)onaspirate 3* 32 12 10 6 7
10:1
3.4:1
Blast (%) Initial diagnosis
Karyotype
ETV6 FISH Mutations
Fusions Treatment
Response to TKI
Not increased* CML with atypical fusion
46,XY,t(9;12)
(q34;p13)[9]/46, XY[11]
Positive
ARID2 TP53 ETV6-ABL1 Imatinib, Dasatinib
Not increased Atypical CML
46,XY,t(9;12)
(q34.1;p13)[16]/ 46,idem,del(7) (q22q36)[1]/46,XY[11] Positive
ARID2 CDKN1B ETV6-ABL1 Dasatinib
Diagnosed in 2005
achieved cytogenetic remission on imatinib; relapsed in 2015, achieved cytogenetic/ molecular remission on dasatinib. Alive
Diagnosed
in 02/2018, achieved cytogenetic/ molecular remission on dasatinib; Alive
4 Myeloid/ lymphoid neoplasm with eosinophilia and gene rearrangement 53,XX,+X,+8, +10,+11,+14, +18,+19[7]/ 46,XX[13]
NA
Absent
ETV6-ABL1
Dasatinib
Marked
improvement
in lymphadenopathy; resolution of eosinophilia, alive
Not increased CML with atypical fusion
46,XY
NA Absent
ETV6-ABL1
Dasatinib
Diagnosed in
10/2018, achieved cytogenetic/ molecular remission on dasatinib; Alive
Not increased Essential thrombocythemia (ET)
46,XX
Positive Absent
ETV6-ABL1
Hydroxyurea, Heat shock protein Inhibitor, ruxolitinib, Anagrelide, interferon Imatinib, cytarabine Treated as ET
in 2011-2016; progressed to AML in 2016 and treated with induction and imatinib died in a month from complications
2 CML
45,XY,-7[17]/
46,idem,+11 [4]
Positive
SETD2 ETV6-ABL1
Nilotinib
Leukocytosis
in 2016, diagnosed
and treated with nilotinib until 2018, progressed
to BALL, achieved remission with HyperCVAD, alive
*At relapse in 2015.WBC: white blood cell count; PLT: platelets; yrs: years; mons: months; M: male; F: female; NA: not available; CML: chronic myeloid leukemia;TKI: tyrosine kinase inhibitor; MPAL: mixed phenotype acute leukemia.
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