Uncovering the pathogenesis of large granular lymphocytic leukemia—novel STAT3 and STAT5b mutations

Figures & data

Figure 1. The protein domains of STAT3α (A) and STAT5b (B) with the mutated amino acids detected in cancer are presented in a linear model.

Figure 2. STAT3 and STAT5b signaling cascade.

Table I. Somatic STAT3 mutations reported in different studies.

	Koskela et al. (9)	Jerez et al. (10)		Fasan et al. (41)		Ohgami et al. (42)			Pilati et al. (44)	Couronne et al. (45)	Hu et al. (47)	Kim et al. (48)	Jerez et al. (52)
Study (ref. no.) Patients in the study	77 T-LGL	120 T-LGL	50 NK-LGL	55 T-LGL	7 NK-LGL	12 ALCL	8 PTCL	36 T-LGL	49 IHCA	79 DLBCL, 258 TCL	40 DLBCL	26,277 cancer patients	151 AA	367 MDS
E166Q									1 (2%)
M206K											1
D502Y									1 (2%)^a
S614R		3 (3%)
E616del										2 (DLBCL)
G618R			1 (2%)
Y640F	13 (17%)	14 (12%)	4 (8%)	18 (33%)			2 (25%)	2 (6%)	1 (2%)	1 (PTCL)			x	x
Q643K												1 (rectal adenoma)
N647I	3 (4%)	1 (1%)	2 (4%)	7 (13%)		1 (8%)
G656D												1 (PTCL)
K658M		1 (1%)		1 (2%)
K658N	1 (1%)
K658Y									1 (2%) ^a
I659L				1 (2%)
D661H	1 (1%)					1 (8%)
D661I			1 (2%)
D661V	7 (9%)	3 (3%)		1 (2%)	1 (14%)
D661Y	7 (9%)	12 (10%)	7 (14%)	13 (24%)	1 (14%)			2 (6%)		1 (ALCL)			x	x
Y657_K658insY	1 (1%)
Y657_M660dup									1 (2%)
Y657dup					1 (14%)
Y657ins										1 (gdTCL)
G656_Y657insF									1 (2%)
D661ins										1 (ALCL)
STAT3 mutations total	33 (43%)	34 (28%)	15 (30%)	41 (75%)	3 (43%)	2 (17%)	2 (25%)	4 (11%)	6 (12%)	6 (2%)	1 (3%)	2 (0.07%)	16 (11%)	18 (5%)

AA = aplastic anemia; ALCL = ALK-negative anaplastic large cell lymphoma; DLBCL = diffuse large B-cell lymphoma; gdTCL = gamma-delta T-cell lymphoma; ICHA = inflammatory hepatocellular adenoma; LGL = large granular lymphocytic leukemia; MDS = myelodysplastic syndrome; PTCL = peripheral T-cell lymphoma; TCL = T-cell lymphoma.

^aMutations D502Y and K658Y in the same patient.

Figure 3. The STAT3 and STAT5b mutations seen in LGL leukemia patients are marked in blue dots in 3D model of STAT3 (A) and STAT5b (B) monomers. The STAT3 monomer is attached to target DNA, which is shown as a blue strand.

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