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Year : 2018  |  Volume : 14  |  Issue : 10  |  Page : 800-802

Trisomy 3 as an acquired cytogenetic abnormality in primary acute megakaryoblastic leukemia

1 MAHAK Pediatric Cancer Treatment and Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Date of Web Publication24-Sep-2018

Correspondence Address:
Narjes Mehrvar
Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.175430

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 > Abstract 

Acute myeloid leukemia has a rare subtype in French-American-British classification as M7 or acute megakaryoblastic leukemia. Chromosome abnormalities in cases with acute megakaryoblastic leukemia can affect their prognosis. Evaluation of these abnormalities and their impact are not fully elucidated. This case presentation is about 16 months female who has a rare abnormality (trisomy 3) alongside acute megakaryoblastic leukemia. The remarkable point is that her malignancy is as primary or non-Down syndrome acute megakaryoblastic leukemia. The author's suggestion through this case presentation is the necessity of drawing a cytogenetic profile, especially in cases with acute megakaryoblastic leukemia for better treatment strategies.

Keywords: Abnormality, acute megakaryoblastic leukemia, trisomy 3

How to cite this article:
Azad VF, Mehrvar A, Mehrvar N. Trisomy 3 as an acquired cytogenetic abnormality in primary acute megakaryoblastic leukemia. J Can Res Ther 2018;14, Suppl S3:800-2

How to cite this URL:
Azad VF, Mehrvar A, Mehrvar N. Trisomy 3 as an acquired cytogenetic abnormality in primary acute megakaryoblastic leukemia. J Can Res Ther [serial online] 2018 [cited 2022 May 26];14, Suppl S3:800-2. Available from: https://www.cancerjournal.net/text.asp?2018/14/10/800/175430

 > Introduction Top

One of the heterogeneous forms of acute myeloid leukemia that presents 10–20% of all cases is acute megakaryoblastic leukemia (AMKL),[1] and according to French-American-British (FAB) classification categorized as the seventh subtype of AML (AML-M7).[2] Two major subgroups of pediatric AMKL are Down syndrome (DS)-AMKL with favorable outcome[3] and primary AMKL (non-DS-AMKL) with poor prognosis.[4]

Major subgroups of non-DS-AMKL with chromosomal abnormality defined as cases with constitutional trisomy 21 with GATA1 mutation, and those with the t(1;22)(p13;q13) encoding OTT-MAL fusion protein that restricted to infants.[4],[5] Apart from foregoing abnormalities, the somatic events in primary AMKL are largely undefined.[3]

This case report presents a patient who diagnosed as non-DS (primary) acute megakaryoblastic leukemia with abnormal cytogenetic report of trisomy 3.

 > Case Report Top

MK, a 16-month-old female without the underlying disease who is a second child of nonconsanguineous parents with no familial history of cancer in her pedigree, referred to Mahak Pediatric Cancer Treatment and Research Center for diagnosis and treatment.

Her chief complaints were severe grippe, periodic fever, pale, and faint for 2 weeks. The clinical examinations at the time of admission were normal. Echocardiography reported prolapse of mitral valves. The laboratory tests showed a decrease in hematology indices (platelet: 29 K/μL, Hgb: 9.7 g/dL, and red blood cell: 3.74 M/μL) and increase in lactate dehydrogenase (2216 IU/L), and erythrocyte sedimentation rate 1st h (79 mm/h).

Her bone marrow sample was analyzed through flow cytometry method in two different centers. Their reports were compatible with acute megakaryoblastic leukemia (AML-M7). [Table 1] shows the percentage of each CD marker expression in those centers.
Table 1: Expression of markers through flow cytometry analysis

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Molecular study for detecting ITD and D835 mutations of Fms-like tyrosine kinase 3 gene, BCR-ABL fusion gene, and ETV6-RUNX1 aberration from bone marrow sample were negative. Bone marrow karyotyping on 10 metaphases spreads by GTG technique at 350–400 band resolution revealed 47 female chromosomes with an extra chromosome 3 and balanced translocation of chromosome 7p15 and 17q25 in three spreads and finally seven remained spreads with normal 46, XX [Figure 1].
Figure 1: 47,XX,+3,t(7;17)(p15;q25)[3]/46,XX[7]

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Therapeutic regimen for this case is according to AML-BFM 98 protocol and at the time of writing the manuscript, she is in the reinduction phase of chemotherapy with a stable condition.

 > Discussion Top

Biologically and according to FAB classification, acute megakaryoblastic leukemia (AMKL) is the heterogeneous form of acute myeloid leukemia (AML).[2] AMKL has a rare incidence, as 1% to 10%, in childhood and adult cases of AML.[6] Primary AMKL (non-Down-Syndrome-AMKL) is more relevant in pediatric cases.[5] Because of difficulty in determining non-DS-AMKL, the diagnosis of these cases depends on reliable referral centers through their valid and accurate diagnostic methods.[2] In this way, there is not any reliable data around the exact number of cases with AMKL.

Abnormalities of chromosome 3 in cases with hematopoietic malignancies are rare compared to other involved chromosomes.[7] Trisomy 3 as a secondary event was shown in some malignancies as mucosa-associated lymphoid tissue.[8] Mapping of chromosome 3 discovered some genes as EVII (Ectopic Viral Insertion Site 1) that expresses in acute myelogenous leukemia[9] and relate with poor prognosis in these cases.[10] Abnormalities of chromosome 3 in patients with AML can be a rare landmark of high-risk profile.[7],[10] The karyotype of children with AML-M7 can be associated with abnormalities of 3q21-3q26.[10] A retrospective study by Liu et al. revealed that abnormalities of chromosome 3 are increasing slightly in cases with acute myeloid leukemia.[7]

AMKL in non-DS patients (primary AMKL) is heterogeneous[1],[2] and appears to have a high relation with t (1;22)(p13;q13).[11] Trisomy 3 is counted as a rare sole abnormality in these cases.[12] Literature and reviews revealed eight cases with AMKL, who had trisomy 3. [Table 2] shows the characteristics of these cases who introduced by different researchers since 1998 up to now.
Table 2: Characteristics of cases with acute megakaryoblastic leukemia and trisomy three

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The balanced rearrangement of t(7;17)(p15;q25) was also detected in this case. Displayed rearrangements about this translocation showed that it was reported in a 71-year-old male with AML-M6.[13] Their results confirmed that abnormalities of chromosome 7 can lead to a poor prognosis of cases with AML.[13] The presentation of this case is in concordance with Hawkins et al.

Following these cases, we are reporting a 16-month-old female patient who had non-DS AMKL with 47, XX,+3, t(7;17)(p15;q25)[3]/46, XX[7]. This rare case report emphasizes that clinically and genetically primary AMKL is a rare malignancy. Cytogenetic of pediatric AMKL can role as a diagnostic evaluation for considering the prognosis and survival outcomes. Some chromosome rearrangements and abnormalities are critical factors for prognosis, outcomes, and follow-up. The authors' suggestion for further investigations is whole genome sequencing and transcriptome analysis of these rare cases.


Authors thank Mrs. Haghighi for her collaboration in laboratory tests.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

 > References Top

Fujino H, Fujita N, Hamamoto K, Oobu S, Kita M, Tanaka A, et al. Ring/marker chromosome derived from chromosome 7 in childhood acute megakaryoblastic leukemia with monosomy 7. Int J Hematol 2010;92:386-90.  Back to cited text no. 1
Athale UH, Razzouk BI, Raimondi SC, Tong X, Behm FG, Head DR, et al. Biology and outcome of childhood acute megakaryoblastic leukemia: A single institution's experience. Blood 2001;97:3727-32.  Back to cited text no. 2
Bourquin JP, Subramanian A, Langebrake C, Reinhardt D, Bernard O, Ballerini P, et al. Identification of distinct molecular phenotypes in acute megakaryoblastic leukemia by gene expression profiling. Proc Natl Acad Sci U S A 2006;103:3339-44.  Back to cited text no. 3
Hama A, Yagasaki H, Takahashi Y, Nishio N, Muramatsu H, Yoshida N, et al. Acute megakaryoblastic leukaemia (AMKL) in children: A comparison of AMKL with and without Down syndrome. Br J Haematol 2008;140:552-61.  Back to cited text no. 4
Malinge S, Ragu C, Della-Valle V, Pisani D, Constantinescu SN, Perez C, et al. Activating mutations in human acute megakaryoblastic leukemia. Blood 2008;112:4220-6.  Back to cited text no. 5
Tallman MS, Neuberg D, Bennett JM, Francois CJ, Paietta E, Wiernik PH, et al. Acute megakaryocytic leukemia: The Eastern Cooperative Oncology Group experience. Blood 2000;96:2405-11.  Back to cited text no. 6
Liu D, Zhang Y, Chen S, Pan J, He X, Liang J, et al. Retrospective evaluation of the clinical and laboratory data from 300 patients of various hematological malignancies with chromosome 3 abnormalities. Cancer Genet 2015;208:333-40.  Back to cited text no. 7
Gruszka-Westwood AM, Matutes E, Coignet LJ, Wotherspoon A, Catovsky D. The incidence of trisomy 3 in splenic lymphoma with villous lymphocytes: A study by FISH. Br J Haematol 1999;104:600-4.  Back to cited text no. 8
Morishita K, Parganas E, William CL, Whittaker MH, Drabkin H, Oval J, et al. Activation of EVI1 gene expression in human acute myelogenous leukemias by translocations spanning 300-400 kilobases on chromosome band 3q26. Proc Natl Acad Sci U S A 1992;89:3937-41.  Back to cited text no. 9
Manola KN. Cytogenetics of pediatric acute myeloid leukemia. Eur J Haematol 2009;83:391-405.  Back to cited text no. 10
Cherkaoui S, Bendari M, Madani A, Quessar A, Benchekroun S. Acute megakaryoblastic leukemia in children: Diagnosis and management challenges in resource-poor countries. Open Cancer J 2014;7:7-10.  Back to cited text no. 11
Dastugue N, Lafage-Pochitaloff M, Pagès MP, Radford I, Bastard C, Talmant P, et al. Cytogenetic profile of childhood and adult megakaryoblastic leukemia (M7): A study of the Groupe Français de Cytogénétique Hématologique (GFCH). Blood 2002;100:618-26.  Back to cited text no. 12
Hawkins JM, Bain B, Mehta AB, Moorman AV. Complex hypodiploidy in acute myeloid leukaemia: A United Kingdom Cancer Cytogenetics Group study. Leuk Res 1995;19:905-13.  Back to cited text no. 13


  [Figure 1]

  [Table 1], [Table 2]

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