Activating STAT5B mutations can cause both primary hypereosinophilia and lymphocyte-variant hypereosinophilia

Figures & data

Figure 1. Microscopic pictures of myeloid neoplasms with STAT5B mutations (A–F) and bone marrow of a patient with peripheral T-cell lymphoma (PTCL)-NOS with STAT5B mutation (G–H). (A) Marrow shows sheets of myeloblasts (Case #1, Bone marrow biopsy, HE ×400), (B) pSTAT5 immunohistochemistry shows immunoreactivity in myeloblasts (Case #1, Bone marrow biopsy, pSTAT5 × 400), (C) eosinophils and precursors are increased (Case #4, Bone marrow biopsy, HE x400), (D) peripheral blood shows increase in eosinophils (Case #4, Peripheral blood, Giemsa x500), (E) eosinophils and precursors are increased (Case #5, Bone marrow biopsy, HE ×400), (F) CD61 highlights numerous dysplastic megakaryocytes (Case #5, Bone marrow biopsy, CD61 × 200), (G) bone marrow shows increased eosinophils and precursors (PTCL-NOS, Bone marrow biopsy, HE ×200), (H) peripheral blood shows increase in eosinophils (PTCL-NOS, Peripheral blood, Giemsa ×500), (I) flow cytometry performed with bone marrow aspirate sample of PTCL-NOS patient shows small abnormal T-cell population with loss of surface CD3 (0.26% of total WBC), consistent with minimal bone marrow involvement by PTCL-NOS. (J) flow sorting was performed with a peripheral blood sample of Case #4 to isolate granulocytes, eosinophils, B-cells and T-cells to further perform NGS in each population, (K) The results of subsequent next generation sequencing in each population of Case #4. STAT5B mutations were identified in granulocytes and eosinophils, but not in B-cells or T-cells.

Table 1. Myeloid neoplasms with STAT5B mutations.

Case #	Age	Gender	Diagnosis by WHO classification	WBC (/mcl)	Eosinophilia (Y/N)	PB eosinophils (%)	PB absolute eosinophil count (/mcl)	BM Blast (%)	Abnormal T-cells by flow cytometry	Karyotype	STAT5B mutation (s) (VAF%)	Therapy	Follow up (months)	Outcome
1	77	F	AML with with mutated NPM1	40300	N	1	400	66	Not detected	46,XX[20]	p.N642H (38.9%)	Decitabine, Enasidenib	12	DOD
2	70	F	AML, therapy-related*	2200	N	4	100	34	ND	46,XX[20]	p.N642H (10.1%)	Cytarabine, daunorubicin, HIDAC	24	AWD
3	71	F	AML, NOS**	8000	N	3	200	8	Not detected	46,X,t(X;9) (p22.1;q34.3) [15]/46,XX[5]	p.N642H (12.2%)	CLAG-M, Enasidenib	30	DOD
4	88	M	MDS-RS-SLD	7100	Y	24	1700	4	Not detected	47,XY,+8[16]/46, idem,-Y[8]/46, XY[1]	p.T628S (5.4%); p.V712E (1.8%)	Decitabine, EPO, G-CSF	60	AWD
5	74	M	CMML	17000	Y	14.7	2500	3	Not detected	46,XY[20]	p.N642H (44.9%)	Observation	10	DOC

AML: acute myeloid leukemia; NOS: not otherwise specified; MDS-RS-SLD: myelodysplasic syndrome with ring sideroblasts and single lineage dysplasia; CMML: chronic myelomonocytic leukemia; PB: peripheral blood; BM: bone marrow; ND: not done; HIDAC: high-dose cytarabine; CLAG-M: Cladribine, Cytarabine, G-CSF, Mitoxantrone; DOD: died of disease; AWD: alive with disease; DOC: died of complications.

*History of marginal zone lymphona, status post chemotherapy.

**Persistent AML, NOS, showing 8% blast in the bone marrow after induction therapy.