kjh The Korean Journal of Hematology Korean J Hematol 1738-7949 2092-9129 Korean Society of Hematology 10.5045/kjh.2007.42.4.397 kjh-42-397 Case Report Two Cases of Acute Leukemic Transformation with a Chromosome 17 Abnormality and p53 Overexpression Evolving from Essential Thrombocythemia ChoYoung-UkM.D. ChiHyun-SookM.D. JangSeongsooM.D. ParkChan-JeoungM.D. SeoEul-JooM.D. LeeJe-HwanM.D. 1 Departments of Laboratory Medicine, Seoul, Korea Internal Medicine, University of Ulsan College of Medicine and Asan Medical Center, Seoul, Korea Correspondence to：Hyun-Sook Chi, M.D. Department of Laboratory Medicine, University of Ulsan College of Medicine and Asan Medical Center 388-1, Pungnap 2-dong, Songpa-gu, Seoul 138-736, Korea Tel: ＋82-2-3010-4502, Fax: ＋82-2-478-0884 E-mail: hschi@amc.seoul.kr 012007 19012007 424397 403 06082007 25102007 05112007 Copyright © 2007 Korean Society of Hematology 2007 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Essential thrombocythemia (ET) is a clonalmyeloproliferative disorder that can rarely transform into acute leukemia in 1∼5% of cases. A recent study has found that a significant proportion of leukemic cases from ET were associated with a cytogenetic abnormality (17p deletion). Herein, we report two cases of acute myeloid leukemic transformations harboring a 17p abnormality from a series of 119 ET patients. The first case, a 48-year-old female, developed acute myeloid leukemia with maturation (AML-M2) accompanying myelodysplasia was diagnosed 6.1 years after the initial diagnosis of ET. She was treated with hydroxyurea. Her karyotype showed a monosomy 17. The second case, a 61-year-old male, developed acute megakaryoblastic leukemia (AML-M7) with a very complex hyperdiploidy including addition of 17p13 that developed 6.5 years after the initial diagnosis. He was treated with hydroxyurea and anagrelide. The immunohistochemistry showed p53 overexpression in both cases. Our cases support the specificity of chromosome 17 abnormality and p53 overexpression in acute leukemic transformation from ET.

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(A) Peripheral blood smear of case 1 shows a pseudo-Pelger Huet anomaly in neutrophil, a blast, and numerous hypogranular platelets (Wright-Giemsa stain, ×1,000). (B) Bone marrow aspiration of case 1 shows dysgranulocytic changes such as pseudo-Pelger Huet anomaly, hypogranularity and bizarre nuclei and proliferation of blasts (Wright-Giemsa stain, ×1,000).

(A) Leukemic cells reveal overexpression of p53 on the biopsy section in case 1 (Immunohistochemistry for p53, ×400). (B) Leukemic cells reveal overexpression of p53 on the biopsy section in case 2. Note the demarcation between leukemic area and hemopoietic area (Immunohistochemistry for p53, ×400).

(A) Peripheral blood smear of case 2 shows a blast (left). Bone marrow aspiration also shows a blast with cytoplasmic pseudopod formation (right) (Wright-Giemsa stain, ×1,000). (B) Bone marrow aspiration of case 2 shows positive reaction to acid phosphatase (left), and positive to alpha naphthyl acetate esterase (right) (Acid phosphatase stain and alpha naphthyl acetate esterase stain, respectively, ×1,000).

(A) Bone marrow biopsy of case 2 shows diffuse infiltration of leukemic cells (left). Marked megakaryocytic hyperplasia is noted in hemopoietic area (right upper) and diffuse extensive fibrosis in fibrotic area (right lower) (H&E stain, ×400). (B) Leukemic cells reveal positive reaction to LCA (left), and negative reaction to MPO (right). (Immunohistochemistry for LCA and anti-MPO, respectively, ×400). (C) Megakaryocytes show positive reaction to CD61 but granulocytic cells reveal negative reaction in case 2 (left). Arrows indicate that leukemic cells are positive for CD61 in case 2 (right) (Immunohistochemistry for CD61, ×400).

Clinical and laboratory features of the two ET cases with evolution into AML

  Case 1 Case 2
Gender/Age∗ F/48 M/61
Interval between ET and AML (years) 6.1 6.5
Duration of HU treatment (years) 6.1 6.1
CBC at leukemic transformation 39,100-7.4-969K 9,800-8.2-431K
FAB subtype M2 (AML with multilineage dysplasia by WHO classification) M7
Pseudo Pelger-Huet anomaly Yes No
Karyotype 45,XX,t(6;14)(p21.3;q32.3), -17,add(20)(q11.2)[20] 57,Y,der(X)t(X;18)(p11.2;q11.2),+6,+8,+8,+9,de (9)(q22)x2,+13,+14,+15,add(17)(p13), der(18)add(18)(p13.3)t(X;18),+19,+idic(21) (p11.2)x2,+mar[15]/46,XY[5]
p53 overexpression† Yes Yes
Induction chemotherapy Ara-C and daunorubicin ND
Clinical results No response to chemotherapy, follow-up loss Supportive care, death
Survival after diagnosis of leukemia (months) 11.9 1.0

∗Age at the diagnosis of ET,

Demonstration by immunohistochemistry. Abbreviations: ET, essential thrombocythemia; AML, acute myeloid leukemia; ND, not done.