Subjects:
BloodWork, Free Research Articles, Myeloid Neoplasia
A 76-year-old man diagnosed with JAK2V617F-positive polycythemia vera (PV) had his blood counts maintained well with phlebotomy and hydroxyurea. Two years later, he complained of increased fatigue and was found to have moderately decreased platelets, which soon progressed to severe thrombocytopenia and mild anemia (leukocytes, 4.9 × 109/L; hemoglobin, 119 g/L; platelets, 29 × 109/L). Blood smear showed circulating “blasts” with deeply basophilic cytoplasm with vacuoles (panel A: ×1000). Bone marrow examination exhibited markedly increased “blasts” with morphology suggestive of proerythroblasts (panel B: aspirate smear, ×1000; panel C: core biopsy, ×400). Immunohistochemistry demonstrated membrane staining for E-cadherin (panel C, inset: ×400). Flow cytometry detected 66% “blasts” that were negative-dim for CD45, expressed bright CD71, HLA-DR (panel D), and dim CD33, and was negative for CD34 and CD117. Cytogenetics demonstrates complex karyotype: 41,XY,-3,-4,add(7)(q22),+del(11)(p11.2),-13,-14,-16,17[2]/40,idem,der(18;21)(q10;q10)[5]. Genomic sequencing analysis revealed pathogenic mutations on TP53: (NM_000546)c.517G>A(p.Val173Met) (62.3%), TET2 (NM_001127208)c.3861delT(p.Phe1287LeufsTer76) (19.5%), and TET2 (NM_001127208)c.5422A>T(p.Arg1808Ter) (26.9%), besides JAK2V617F (61.2%). The diagnosis of pure erythroid leukemia (PEL) evolved clonally from PV was established, and chemotherapy was started. The patient died 2 weeks after diagnosis of transformation to PEL resulting from multiorgan failure.
View largeDownload PPT

A 76-year-old man diagnosed with JAK2V617F-positive polycythemia vera (PV) had his blood counts maintained well with phlebotomy and hydroxyurea. Two years later, he complained of increased fatigue and was found to have moderately decreased platelets, which soon progressed to severe thrombocytopenia and mild anemia (leukocytes, 4.9 × 109/L; hemoglobin, 119 g/L; platelets, 29 × 109/L). Blood smear showed circulating “blasts” with deeply basophilic cytoplasm with vacuoles (panel A: ×1000). Bone marrow examination exhibited markedly increased “blasts” with morphology suggestive of proerythroblasts (panel B: aspirate smear, ×1000; panel C: core biopsy, ×400). Immunohistochemistry demonstrated membrane staining for E-cadherin (panel C, inset: ×400). Flow cytometry detected 66% “blasts” that were negative-dim for CD45, expressed bright CD71, HLA-DR (panel D), and dim CD33, and was negative for CD34 and CD117. Cytogenetics demonstrates complex karyotype: 41,XY,-3,-4,add(7)(q22),+del(11)(p11.2),-13,-14,-16,17[2]/40,idem,der(18;21)(q10;q10)[5]. Genomic sequencing analysis revealed pathogenic mutations on TP53: (NM_000546)c.517G>A(p.Val173Met) (62.3%), TET2 (NM_001127208)c.3861delT(p.Phe1287LeufsTer76) (19.5%), and TET2 (NM_001127208)c.5422A>T(p.Arg1808Ter) (26.9%), besides JAK2V617F (61.2%). The diagnosis of pure erythroid leukemia (PEL) evolved clonally from PV was established, and chemotherapy was started. The patient died 2 weeks after diagnosis of transformation to PEL resulting from multiorgan failure.

PEL transformed from PV is extremely rare, and pathogenesis is unclear. In our case, the acquisition of a TP53 mutation likely produced a “double-hit” effect with the JAK2V617F-positive clone to drive this leukemic transformation in the erythroid lineage.

A 76-year-old man diagnosed with JAK2V617F-positive polycythemia vera (PV) had his blood counts maintained well with phlebotomy and hydroxyurea. Two years later, he complained of increased fatigue and was found to have moderately decreased platelets, which soon progressed to severe thrombocytopenia and mild anemia (leukocytes, 4.9 × 109/L; hemoglobin, 119 g/L; platelets, 29 × 109/L). Blood smear showed circulating “blasts” with deeply basophilic cytoplasm with vacuoles (panel A: ×1000). Bone marrow examination exhibited markedly increased “blasts” with morphology suggestive of proerythroblasts (panel B: aspirate smear, ×1000; panel C: core biopsy, ×400). Immunohistochemistry demonstrated membrane staining for E-cadherin (panel C, inset: ×400). Flow cytometry detected 66% “blasts” that were negative-dim for CD45, expressed bright CD71, HLA-DR (panel D), and dim CD33, and was negative for CD34 and CD117. Cytogenetics demonstrates complex karyotype: 41,XY,-3,-4,add(7)(q22),+del(11)(p11.2),-13,-14,-16,17[2]/40,idem,der(18;21)(q10;q10)[5]. Genomic sequencing analysis revealed pathogenic mutations on TP53: (NM_000546)c.517G>A(p.Val173Met) (62.3%), TET2 (NM_001127208)c.3861delT(p.Phe1287LeufsTer76) (19.5%), and TET2 (NM_001127208)c.5422A>T(p.Arg1808Ter) (26.9%), besides JAK2V617F (61.2%). The diagnosis of pure erythroid leukemia (PEL) evolved clonally from PV was established, and chemotherapy was started. The patient died 2 weeks after diagnosis of transformation to PEL resulting from multiorgan failure.
View largeDownload PPT

A 76-year-old man diagnosed with JAK2V617F-positive polycythemia vera (PV) had his blood counts maintained well with phlebotomy and hydroxyurea. Two years later, he complained of increased fatigue and was found to have moderately decreased platelets, which soon progressed to severe thrombocytopenia and mild anemia (leukocytes, 4.9 × 109/L; hemoglobin, 119 g/L; platelets, 29 × 109/L). Blood smear showed circulating “blasts” with deeply basophilic cytoplasm with vacuoles (panel A: ×1000). Bone marrow examination exhibited markedly increased “blasts” with morphology suggestive of proerythroblasts (panel B: aspirate smear, ×1000; panel C: core biopsy, ×400). Immunohistochemistry demonstrated membrane staining for E-cadherin (panel C, inset: ×400). Flow cytometry detected 66% “blasts” that were negative-dim for CD45, expressed bright CD71, HLA-DR (panel D), and dim CD33, and was negative for CD34 and CD117. Cytogenetics demonstrates complex karyotype: 41,XY,-3,-4,add(7)(q22),+del(11)(p11.2),-13,-14,-16,17[2]/40,idem,der(18;21)(q10;q10)[5]. Genomic sequencing analysis revealed pathogenic mutations on TP53: (NM_000546)c.517G>A(p.Val173Met) (62.3%), TET2 (NM_001127208)c.3861delT(p.Phe1287LeufsTer76) (19.5%), and TET2 (NM_001127208)c.5422A>T(p.Arg1808Ter) (26.9%), besides JAK2V617F (61.2%). The diagnosis of pure erythroid leukemia (PEL) evolved clonally from PV was established, and chemotherapy was started. The patient died 2 weeks after diagnosis of transformation to PEL resulting from multiorgan failure.

PEL transformed from PV is extremely rare, and pathogenesis is unclear. In our case, the acquisition of a TP53 mutation likely produced a “double-hit” effect with the JAK2V617F-positive clone to drive this leukemic transformation in the erythroid lineage.

Close modal

For additional images, visit the ASH Image Bank, a reference and teaching tool that is continually updated with new atlas and case study images. For more information, visit http://imagebank.hematology.org.

© 2022 by The American Society of Hematology
2022
Sign in via your Institution