Table 2. Clinical, pathological, and genetic features of patients who developed aggressive B-cell lymphomas during JAK1/2 inhibition.

	Patient 1 (Vienna)	Patient 2 (Vienna)	Patient 3 (Vienna)	Patient 4 (Vienna)	Patient 5 (Paris)	Patient 6 (Paris)
Sex	Female	Female	Female	Male	Female	Female
MPN	PV post-PV MF	PMF	PMF	PMF	ET post-ET MF	PMF
Age at MPN	22 (PV)	45	71	70	66 (ET)	50
	54 (post-PV MF)				69 (post-ET MF)
JAK2V617 F mutation in MPN	Positive	Positive	Positive	Positive	Negative (CALR mutation)	Positive
Treatment before JAK1/2 inhibition	Phlebotomy	Anagrelide Hydroxyurea	Hydroxyurea	None	Anagrelide	None
	Intron A				Hydroxyurea
	Pipobroman				Pipobroman
	Hydroxyurea				EPO
JAK1/2 inhibitor	Ruxolitinib	Ruxolitinib	Fedratinib Ruxolitinib	Ruxolitinib	Ruxolitinib	Ruxolitinib
Time from diagnosis of MPN to diagnosis of NHL, years	35 (PV to NHL)	14	2	4	6 (ETto NHL)	3
	3 (post-PV MF to NHL)				3 (post-ET MF to NHL)
Time (months) from JAK1/2 inhibition to diagnosis of NHL	20	35	13	30	17	28
Age at NHL	57	59	73	74	72	53
NHL	HGBL	DLBCL	DLBCL	DLBCL	DLBCL	DLBCL
Antilymphoma treatment	Burkitt Protocol, Buparlisib (BKM120)	EPOCH-R R-CHOP	R-CHOP	R-CHOP	R-CHOP	R-CHOP
Outcome	PD, Death	CR ongoing	CRu, early relapse, death	CRu, sAML, death	CR	PR, Death
NHL manifestation	BM, PB, LN	BM, PB, LN	Mammary gland; at relapse: >BM, PB	Mucosa	LN	BM
COO	Not applicable	GCB	Non-GCB	Non-GCB	Non-GCB	Non-GCB
CS/IPI	IV E / 4-5	IV E/2	II E / 3	I E / 2	II / 2	IV E/2
DHS	2	2	2	1
IHC						Negative
MYC (40%)	85%	80%	80%	70%	Negative
BCL2 (50%)	100%	100%	100%	5%	Positive
BCL6 (30%)	2%	80%	40%	40%	Positive
p53 (30%)	100%	80%	80%	70%
FISH
MYC	Translocation	Translocation	Normal	Normal
BCL2	Amplification	Translocation	Normal	Normal
BCL6	Normal	Translocation	n.d.	Translocation
TPS3	Deletion	Normal	Normal	Normal
Targeted sequencing	TMB: low (2 m/mb)	TMB: high (22 m/mb)	n.d.	n.d.	n.d.	n.d.
	IGH-MYC rearrangement	IGH-BCL2 rearrangement
	CDK6 amplification	MYC A59T, SOCS1-MYC rearrangement
	MLL2 R5086*	CDKN2A p14ARF C15fs*28, p14ARF M1V
	TP53 A159P	BCL2 P59S, R129H
		TNFRSF14 T169fs*65
		KRAS G13D
		B2M L15fs*41 BCL7A splice site 92 + 1G>A
		FAS splice site 664_676+36del49
		TAF1 R1049H
JAK2V617F Mutation in NHL	Negative	Negative	Negative	Negative	n.d.	n.d.
Detection of preexisting B-cell clone	Yes	Yes	Not applicable	Yes

COO, cell of origin; CR, complete remission; CRu, complete remission unconfirmed; CS, clinical stage according to Ann-Arbor classification; DHS, double-hit protein score; DLBCL, diffuse large B-cell lymphoma; E, extranodal; EPOCH-R, immunochemotherapy (etoposide, doxorubicin, cyclophosphamide, vincristine and prednisone with rituximab); FISH, fluorescent in-situ hybridization; GCB, germinal center B-cell like; HGBL, high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement; IHC, immunohistochemistry; IPI, international prognostic index; LN, lymph node; m/mb: mutations per megabase; n.d., not done; NGS, new-generation sequencing; non-GCB, nongerminal center B-cell like; PD, progressive disease; post-ET MF, postessential thrombocythemia myelofibrosis; post-PV MF, postpolycythemia vera myelofibrosis; R-CHOP: immunochemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone); sAML, secondary acute myeloid leukemia; TMB, tumor mutation burden.