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Myeloid neoplasm with t(3;8)(q26;q24): report of six cases and review of the literature a

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Xiangdong Xu , Mu Su , Norman B. Levy , Arash Mohtashamian , Sara Monaghan , Prabhjot c

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Kaur , Charles Zaremba , Rolando Garcia , H. Elizabeth Broome , Marie L. Dell’Aquila & e

Huan-You Wang a

Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA b

Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

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Department of Pathology, Dartmonth-Hitchcook Medical Center, Lebanon, NH, USA

d

Department of Pathology, Naval Medical Center, San Diego, CA, USA

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Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA Published online: 01 Jun 2015.

To cite this article: Xiangdong Xu, Mu Su, Norman B. Levy, Arash Mohtashamian, Sara Monaghan, Prabhjot Kaur, Charles Zaremba, Rolando Garcia, H. Elizabeth Broome, Marie L. Dell’Aquila & Huan-You Wang (2014) Myeloid neoplasm with t(3;8)(q26;q24): report of six cases and review of the literature, Leukemia & Lymphoma, 55:11, 2532-2537, DOI: 10.3109/10428194.2013.878460 To link to this article: http://dx.doi.org/10.3109/10428194.2013.878460

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Leukemia & Lymphoma, November 2014; 55(11): 2532–2537 © 2014 Informa UK, Ltd. ISSN: 1042-8194 print / 1029-2403 online DOI: 10.3109/10428194.2013.878460

ORIGINAL ARTICLE: CLINICAL

Myeloid neoplasm with t(3;8)(q26;q24): report of six cases and review of the literature Xiangdong Xu1*, Mu Su2*, Norman B. Levy3, Arash Mohtashamian4, Sara Monaghan2, Prabhjot Kaur3, Charles Zaremba2, Rolando Garcia2, H. Elizabeth Broome5, Marie L. Dell’Aquila5 & Huan-You Wang5 1Department of Pathology and Immunology, Washington University in St. Louis, St. Louis, MO, USA, 2Department of Pathology,

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University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA, 3Department of Pathology, Dartmonth-Hitchcook Medical Center, Lebanon, NH, USA, 4Department of Pathology, Naval Medical Center, San Diego, CA, USA and 5Department of Pathology, University of California San Diego Health System, La Jolla, CA, USA

of megakaryocytes with dysplastic features, short duration of the MDS phase, resistance to chemotherapy, short survival and poor prognosis [3]. 3q26 involvement in non-random recurrent balanced translocations also includes t(1;3) (p36;q21), t(2;3)(p13;q26), t(3;4)(q26;q33), t(3;6)(q26;q14), t(3;7)(q26;q21), t(3;8)(q21;q24), t(3;8)(q26;q24), t(3;12) (q26;p11), t(3;12)(q26.2;p13), t(3;17)(q26;q22) and t(3;21) (q26;q22) [4–7]. t(3;8)(q26;q24) is an extremely rare non-random recurrent balanced chromosomal translocation accounting for 0–3.5% (2/57) of myeloid malignancies with 3q rearrangements [5–7]. Literature describing t(3;8)(q26;q24) is very limited, but based on the published English literature, patients with t(3;8)(q26;q24) show overlapping features with those carrying other types of 3q26 abnormalities, such as multilineage dysplasia, association with monosomy 7 [8] and a poor prognosis [9]. In order to better characterize the clinical and morphologic features, associated other genetic abnormalities and clinical course in patients with t(3;8)(q26;q24), we report six additional cases of myeloid neoplasms with t(3;8) (q26;q24). To our best knowledge, this is the largest single collection of myeloid neoplasms with t(3;8)(q26;q24).

Abstract Balanced translocation between chromosomes 3q26 and 8q24 is a very rare event. Here we report six patients with t(3;8) (q26;q24) either as a sole or as a part of genetic abnormalities. Five of the six patients were men with ages ranging from 41 to 84 years old. One patient had a long history of granulocyte colony stimulating factor (G-CSF) treatment. Three of the patients were initially diagnosed with acute myeloid leukemia, two with myelodysplastic syndrome and one with chronic myelogenous leukemia with blast crisis. The peripheral blood in all patients showed severe to moderate anemia; one had absolute neutropenia, one with neutrophilia; four had thrombocytopenia, two with thrombocytosis. The bone marrows from all patients showed dysmegakaryopoiesis with additional erythroid (three patients) and granulocytic (two patients) dysplasia. Cytogenetics revealed t(3;8)(q26;q24) as the sole abnormality in three patients. The majority of patients (4/6) had a poor clinical course, with an average survival of 10 months. Keywords: Acute myeloid leukemia, myeloid dysplastic syndrome, t(3;8)(q26;q24), EVI1, MDS1

Introduction

Clinical history

Rearrangements of chromosome 3 at bands q21 and q26 in the form of inversion [inv(3)(q21q26.2)] or reciprocal translocation [t(3;3)(q21;q26)] have been identified in approximately 1–2% of acute myeloid leukemia (AML) and 3% of de novo or therapy-related myelodysplastic syndrome (MDS/t-MDS) [1,2]. Patients harboring inv(3)(q21q26.2) and t(3;3)(q21;q26), collectively termed the “3q21q26 syndrome,” have characteristic clinical and pathologic features including anemia, normal to elevated platelet counts, hyperplasia

Patient 1 was a 51-year-old man who presented with fatigue and weakness in November 2008. A bone marrow biopsy 1 month later showed AML, not otherwise specified (NOS). After a protracted course, he achieved complete remission 8 months after initial diagnosis in July 2009, followed by allogeneic bone marrow transplant 1 month later. His leukemia relapsed 6 months later. After treatment with cladribine, cytarabine and mitoxantrone, and granulocyte colony stimulating factor (G-CSF), he also received a donor

*Present addresses: Xiangdong Xu, Department of Pathology, VA San Diego Healthcare System, University of California San Diego, San Diego, CA, USA; Mu Su, Department of Pathology, Saint Barnabas Medical Center, Livingston, NJ, USA Correspondence: Huan-You Wang, Department of Pathology, University of California San Diego Health System, 3855 Health Sciences Center, San Diego, CA 92093-0987, USA. Tel: 858-822-2538. Fax: 858-822-1415. E-mail: [email protected] Received 24 October 2013; revised 9 December 2013; accepted 16 December 2013

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Myeloid neoplasm with t(3;8)(q26;q24) lymphocyte infusion in March 2010. He again relapsed in April 2010, and was last treated with salvage therapy including clofarabine and etoposide. Despite the aggressive therapy, the patient expired 3 months later. Patient 2 was a 41-year-old man who presented with a 5-year history of pancytopenia and 7-year history of neutropenia. His past medical history was significant, including multidrug-resistant human immunodeficiency virus (HIV) infection diagnosed 20 years previously. The patient had been receiving G-CSF treatment for his neutropenia for 7 years. A bone marrow biopsy in early 2007 to evaluate pancytopenia revealed a normal karyotype and normocellular marrow with no evidence of dysplasia. A subsequent bone marrow biopsy performed in the middle of 2009 showed dyserythropoiesis and dysmegakaryopoiesis with no increase in myeloid blasts, consistent with refractory cytopenia with multilineage dysplasia (RCMD). No therapy was initiated. The patient was last seen in August 2010, and died of acquired immune deficiency syndrome (AIDS)-related complications shortly afterward. Patient 3 was an 84-year-old man who presented in May 2009 with anemia, thrombocytopenia and fatigue. A bone marrow biopsy at that time revealed 7% myeloid blasts, dyserythropoiesis and dysmegakaryopoiesis, consistent with refractory anemia with excess blasts type 1 (RAEB-1). A second marrow biopsy performed 5 months later showed fibrosis. He was treated with lenalidamide and prednisone, and showed a good initial response. However, he presented in late 2009 with mental status changes, fever and hypotension, and died soon afterward. An autopsy was not performed. Of note, this case has been published [10]. Patient 4 was a 71-year-old woman who, in early 2006, presented with pancytopenia, wheezing and pleuritic chest pain. A bone marrow biopsy at that time showed AML, NOS. The patient elected to have supportive therapy only, and she died 2 months after the initial diagnosis. Patient 5 was a 64-year-old previously healthy man who presented with fatigue, generalized malaise and dyspnea on exertion to an outside hospital in August 2012. A peripheral blood smear showed numerous circulating blasts. A bone marrow biopsy performed 1 month later showed AML with dysplasia-related changes. The disease was refractory to various remedies of chemotherapy. Complete remission was finally achieved after a 10/10 matched unrelated allogeneic stem cell transplant in March 2013. The patient remained disease-free 6 months following a stem cell transplant at the time of last follow-up, 6 months after the transplant. Patient 6 was a 52-year-old man with T7 paraplegia and chronic myelogenous leukemia (CML), who was treated with Gleevec at 400 mg daily for an unknown period of time before presenting with increased myeloid blasts (25% in the bone marrow) in July 2013. At that time he was switched to dasatinib at 100 mg daily due to his gastrointestinal upset related to Gleevec.

Materials and methods

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participating institution. The clinical and treatment histories were obtained from review of medical records.

Peripheral blood smears, bone marrow aspirates and biopsies Peripheral blood and bone marrow aspirate smears were stained with Wright–Giemsa, and bone marrow trephine biopsies were stained with hematoxylin and eosin (H&E), according to the standard protocol. The final diagnosis of each case was made according to the established criteria outlined by the 2008 World Health Organization (WHO) classification of hematopoietic and lymphoid tissues [1,2]. The international prognostic scoring system (IPSS) score in cases of MDS was calculated according to published criteria [2].

Conventional cytogenetics Conventional karyotyping of bone marrow aspirates at the initial and last diagnosis using G-banding was performed according to established methods. Cytogenetic abnormalities were classified according to the International System for Human Cytogenetic Nomenclature [11].

Results Demographic features The demographic data from these six patients are summarized in Table I. There were five men and one woman. The patients’ ages ranged from 41 to 84, with an average of 61 years. While none of the patients had received any prior chemotherapy, patient 2 had received G-CSF treatment for 7 years for his neutropenia and patient 6 received Gleevec for his CML.

Peripheral blood and bone marrow findings All patients (6/6) showed moderate to severe anemia, ranging from 5.6 to 9.8 g/dL of hemoglobin. While four patients (4/6) (patients 1–4) had variable degrees of thrombocytopenia, two patients (2/6) (patients 5 and 6) showed thrombocytosis, and only one patient (1/6) (patient 2) exhibited neutropenia (Table I). Peripheral blood smears showed granulocytic dysplasia in only two patients (patients 1 and 5) [Figure 1(A)]. Cytomorphologic examination of the bone marrow aspirates revealed megakaryocytic [Figure 1(B)] dysplasia in all patients (6/6), with dyserythropoiesis [Figure 1(C)] in three patients (3/6) (patients 1–3) and dysgranulopoiesis in two patients (2/6) (patients 1 and 5). Due to the presence of pancytopenia and erythroid and megakaryocytic dysplasia, patient 2 was diagnosed as having RCMD. Patient 3 was diagnosed with RAEB-1 because of 7% myeloid blasts in the bone marrow aspirate. Three patients (3/6) (patients 1, 4 and 5) had more than 20% myeloid blasts, consistent with AML. Since patient 6 had 25% myeloid blasts, he was diagnosed as having CML in blast phase. The peripheral blood and bone marrow findings are listed in Table I.

Patient selection

Cytogenetic findings

The presence of t(3;8)(q26;q24) was used as a criterion in searching the hematopathology databases of each

Conventional karyotyping (Table II) on bone marrow aspirates revealed t(3;8)(q26;q32) as the sole abnormality in

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Table I. Clinicopathologic features of six patients with myeloid neoplasms harboring t(3;8)(q26;q24).

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Patient 1

Patient 2

Age/sex Presenting symptoms Prior chemotherapy G-CSF treatment prior to diagnosis Hemoglobin (g/dL) WBC (⫻ 109/L) Platelets (⫻ 109/L) Dysplasia in bone marrow

51/M Anemia and thrombocytopenia No

41/M Pancytopenia

Patient 3

Patient 4

Patient 5

Patient 6

No

84/M 71/F Anemia and Pancytopenia thrombocytopenia No No

64/M 52/M Anemia and Anemia, neutrophilia thrombocytosis and thrombocytosis No No

No

Yes

No

No

No

No

9.8

9.0

8.8

5.6

7.1

7.7

4.9 75 Trilineage (⬍ 50%)

1.2 4.37 62 138 Erythroid and Erythroid and megakaryocytic megakaryocytic

Megakaryocytic hyperplasia Blasts (%) in peripheral blood Blasts (%) in bone marrow Diagnosis

Absent

Present

43

IPSS Status at last follow-up

NA 1.0 Dead (19 months after Dead (14 months initial diagnosis) after initial diagnosis)

60.9 442 Megakaryocytic

Present

3.32 5.5 120 469 Megakaryocytic Granulocytic and megakaryocytic (⬎ 50%) Present Present

0

0

6

61

25.5

67

1

7

32.6

61

25

AML, NOS

RCMD

RAEB-1

AML, NOS

Absent

AML with CML in blast phase dysplasia-like changes 1.5 NA NA NA Dead (6 months after Dead (2 months Status postAlive with disease initial diagnosis) after initial allogeneic stem diagnosis) cell transplant and diseasefree 6 months after initial diagnosis

G-CSF, granulocyte colony stimulating factor; WBC, white blood cells; IPSS, international prognostic scoring system score; M, male; F, female; AML, NOS acute myeloid leukemia, not otherwise specified; RCMD, refractory cytopenia with multilineage dysplasia; RAEB-1, refractory anemia with excess blasts type 1; CML, chronic myelogenous leukemia; NA, not available.

Figure 1. (A) Bone marrow aspirate from patient 1 showed a dysplastic segmented neutrophil (pseudo Pelger–Huet) among numerous myeloid blasts (Wright–Giemsa. original magnification ⫻ 500). (B) Bone marrow aspirate from patient 2 showed terminal dyserythropoiesis (Wright– Giemsa, original magnification ⫻ 1000); (C) Bone marrow core biopsy from patient 2 showed prominent dysmegakaryopoiesis (H&E, original magnification ⫻ 400).

Myeloid neoplasm with t(3;8)(q26;q24) Table II. Conventional karyotypic findings of bone marrow aspirates. Patient 1 2 3 4 5 6

Karyotype 46,XY,t(3;8)(q26;q24)[22] 46,XY,t(3;8)(q26;q24)[10]/46,XY[11] 47,XY,t(3;8)(q26;q24),⫹ 14[11]/46,XY[1] 46,XX,t(3;8)(q26.2;q24.1)[11]/46,idem,del(7) (p11.2p15)[2]/45,idem,i(7)(q10) [cp2]/46,XX[6] 46,XY,t(3;8)(q26;q24)[20] 46,XY,t(3;8)(q26;q24),t(9;22)(q34;q11.2) [19]/92,idemx2[1]

three cases (3/6) (patients 1, 2 and 5) (Figure 2), with the remaining three patients (3/6) (patients 3, 4 and 6) harboring additional genetic abnormalities. Patient 3 had trisomy 14, patient 4 had chromosome 7 abnormalities involving both the short and long arms, including deletion of 7p11.2→p15 and isochromosome 7q10, and patient 6 had Philadelphia chromosome.

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Disease progression and survival data The majority (4/6) (patients 1–4) of the patients died within 2–19 months after the initial diagnosis, with an average survival of 10 months (Table I). Patients 1 and 4 died of leukemia and leukemia as well as chronic obstructive pulmonary disease, respectively. Patient 2 died of AIDS-related complications, and patient 3 died of hypotension and fever. Patient 5 remained free of disease 3 months after allogeneic stem cell transplant, and patient 46 is alive with disease.

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Discussion We report six cases of t(3;8)(q26;q24)-containing myeloid neoplasms, including three cases of AML, two cases of MDS and one case of CML in blast phase. The average age for this cohort is 61 years. All patients showed anemia and megakaryocytic dysplasia, but only three cases (3/6) (patients 1–3) showed additional erythroid dysplasia. t(3;8)(q26; q32) was the sole cytogenetic abnormality in three patients (3/6) (patients 1, 2 and 5), while the remaining three patients (3/6) had additional cytogenetic abnormalities. Four patients (4/6) (patients 1–4) died 2–19 months after the initial diagnosis, with an average survival of 10 months. Patient 2 is the first HIV(⫹) patient harboring t(3;8)(q26;q32), and represents the second reported case in which the patient had received long-term G-CSF treatment [12]. In contrast to the previously reported cases ([7,8,12] and Table III), none of our six cases had monosomy 7. To the best of our knowledge, this is the largest cohort including patients with t(3;8)(q26;q24). The relationship between HIV infection and t(3;8) (q26;q24) as seen in patient 2 is not clear. While this could represent a purely coincidental finding, the causal effects of other factors in this patient such as viral (HIV, cytomeglovirus [CMV] and Kaposi sarcoma virus) infection, mycobacterial infection and anti-retroviral medication in isolation or in combination cannot be ruled out. It is of interest to point out, nevertheless, that this patient is the second reported case of myeloid neoplasia in which t(3;8)(q26;q24) occurred

Figure 2. Conventional karyotype from patient 2 showed t(3;8) translocation involving 3q26 and 8q24.

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Table III. Summary of AML, MDS or CMML with t(3;8)(q26;q24) from the English literature. No. of cases

Diagnosis

2

AML

5

AML or MDS

1

CMML

1

AML

1 1

RAEB-2 CML-BP

Cytogenetics

Reference

46,XX,t(3;8)(q26;q24),7[15]/46,XX[5] 46,XX,t(3;8)(q26;q24),del(5q) (q14q34),⫺ 7,⫺ 18[20] 46,XX,t(3;8)(q26;q24),⫺ 7,⫹ mar[20]

[7]

46,XX,t(3;8)(q26;q24)[18]/46,XX[2] 45,XY,t(3;8)(q26;q24),⫺ 7[14] 47,XY,t(3;8)(q26;q24),⫹ 13[13] 46,XY,t(3;8)(q26;q24)[20] 46,XX,t(3;8)(q26;q24) [16]/46,idem,t(8;21)(q13;q22) [2]/45,idem,⫺ 7[2] 45,XY,t(3;8) (q26;q24),⫺ 7[33]/46,XY[1] 46,XY,t(3;8)(q26;q24)[26] 46,XX,t(3;8) (q26.2;q24.1),idem,t(9;22) (q34;q11.2)[15]/46,idem,t(4;5) (p16;q31)[2] /46,idem,del(6) (q21q27)[3]

[8]

[9] [12] [14] [15]

AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; CMML, chronic myelomonocytic leukemia; RAEB-2, refractory anemia with excess blasts type 2; CML-BP, chronic myelogenous leukemia in blast phase.

in a setting of long-standing G-CSF treatment (more than 5 years) [12]. It is, however, the first reported case in this setting in which t(3;8)(q26;q24) was the sole cytogenetic aberrancy. Although Schroeder et al. speculated that G-CSF might also contribute to the development of myeloid malignancies in glycogen storage disease [12], a systemic literature review by Lyman and Kuderer [13] on the risk of AML or MDS associated with G-CSF treatment since its introduction into clinical use 20 years ago failed to confirm this notion [13]. Thus, more cases are needed to address the relationship between long-term G-CSF treatment and t(3;8)(q26;q24). Translocation t(3;8)(q26;q32) is a very rare event. Since its first report in 1987 [14], there have been only 11 reported cases in the English literature [7–9,12,14,15]. Together with our reported six cases, there are a total of 17 cases of myeloid neoplasms harboring t(3;8)(q26;q24). As shown in Tables II and III, t(3;8)(q26;q24) occurs in a variety of genetic conditions: as a primary and sole cytogenetic event (patients 1, 2 and 5 and [8,14], 6/17) or in association with monosomy 7 ([7,8,9,12], 6/17) in 35% of patients, respectively, or as part of complex genetic abnormalities (defined as three or more) in 24% of patients (patient 4 and [7,9,15], 4/17), or as a secondary event in 12% of patients (patient 6 and [15], 2/17). Equally important, t(3;8)(q26;q24) is associated with a broad spectrum of myeloid neoplasms including AML [7,8,12], MDS [8,14], MDS/myeloproliferative neoplasm (MPN) [9] and MPN [15]; both cases in the last category happened to be CML in blast phase (patient 6 and [15]). Monosomy 7 was not present in any of our six patients, in contrast to the reported cases [7,8,9,12], but other chromosome 7 abnormalities were observed here. Deletion 7p11.2→p15 [del(7)(p11.2p15)] and isochromosome 7q10 [i(7)(q10)] were observed in patient 4 (Table II). del(7) (p11p15) has been reported in Philadelphia-positive CML [16] and various subtypes of non-Hodgkin lymphoma [17], indicating that this might be a non-random secondary

event [17]. i(7)(q10) is one of the most commonly acquired cytogenetic abnormalities found in Shwachman–Diamond syndrome [18], and the presence of i(7)(q10) is associated with increased risk of developing MDS in this patient population [19,20]. In addition, i(7)(q10) is observed in other forms of hematolymphoid malignancies, including MDS/AML [21]. However, patient 4 is the first reported patient in which i(7) (q10) and t(3;8)(q26;q24) were concurrently identified. t(3;8)(q26;q24) is perhaps the rarest form of the many types of chromosomal translocation involving the 3q26 locus in association with myeloid neoplasms. Other forms of chromosomal translocation involving 3q26 include inv(3)(q21q26), t(3;3)(q21;q26.2), t(3;12)(q26;p13), t(3;15) (q26;q13), t(3;17)(q26;q22) and t(3;21)(q26.2;q22.1) [3,5–7]. The chromosome 3q26 locus contains two related genes, MDS1 and EVI1 [22], which generate three different proteins, including EVI1, MDS1 (myelodysplasia syndrome 1) and MDS/EVI1. Intriguingly, The EVI1 protein is produced via selecting a translational start site within exon 3. The longer form, the MDS1/EVI1 protein, is produced by intergenic inframe splicing between the MDS1 gene and EVI gene [23]. Lennon et al. have shown that EVI1 is deregulated in patients with translocation involving 3q26 [24]. The breakpoint on chromosome 8 is distal to the PVT1 oncogene homolog, a C-MYC activator in mice [24]. Overexpression of EVI1 protein has often been observed in cases with 3q26 rearrangement, and is associated with a poor prognosis [25,26]. The forced expression of EVI1 in murine embryonic stem cells resulted in the differentiation of abnormally high numbers of megakaryocytic colonies, consistent with the findings often seen in patients with 3q26 rearrangements [27]. However, up-regulated EVI1 expression has been observed in a significant fraction of myeloid malignancies devoid of detectable 3q26 by conventional cytogenetics [26]. This puzzle was partially solved by several recent studies revealing different mechanisms underlying the observed EVI1 overexpression. Lugthart et al. showed that 21% (7/33) of cases of de novo AML with EVI1 overexpression had cryptogenic 3q26 breakpoints detected by fluorescence in situ hybridization (FISH) analysis but not by conventional cytogenetics [26], suggesting that the prevalence of 3q26 abnormalities is higher than previously thought. Arai et al. reported that EVI1 was up-regulated by the MLL–ENL (mixed lineage leukemia–eleven nineteen leukemia) fusion protein exclusively in undifferentiated hematopoietic cells [28]. Vazquez et al. suggested that EVI1 expression is regulated by DNA methylation and acetylation [29], indicating other mechanisms by which EVI1 regulation could be perturbed in myeloid malignancies. In summary, we report six additional cases of myeloid neoplasms with t(3;8)(q26;q24) either as a sole genetic abnormality or as part of genetic aberrancies. Morphologically all six cases showed anemia and megakaryocytic dysplasia with or without dysplasia in other lineage(s). While four (4/6) patients had variable degrees of thrombocytopenia, the remaining two patients (2/6) showed thrombocytosis. Based on this limited cohort, four patients (4/6) died shortly after the initial diagnosis with a median survival of 10 months, indicating that t(3;8)(q26;q24) carries a poor prognosis. It is

Myeloid neoplasm with t(3;8)(q26;q24) our opinion that t(3;8)(q26;q24) should be included as one of the balanced translocations associated with MDS at initial diagnosis. More cases are needed to investigate whether patients with MDS with t(3;8)(q26;q24) have a shorter interval to transformation into AML.

Acknowledgement The authors would like to thank Dr. Anmaar Abdul-Nabi of the Department of Pathology, Washington University in St. Louis, for providing additional follow-up information for patient 5. Potential conflict of interest: Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal.

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Myeloid neoplasm with t(3;8)(q26;q24): report of six cases and review of the literature.

Balanced translocation between chromosomes 3q26 and 8q24 is a very rare event. Here we report six patients with t(3;8)(q26;q24) either as a sole or as...
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