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 ::  Abstract
 :: Introduction
 :: Case Reports
 :: Discussion
 ::  References
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  Table of Contents     
CASE SERIES
Year : 2018  |  Volume : 64  |  Issue : 2  |  Page : 109-111

3q26 chromosomal anomalies in acute myeloid leukemia: First descriptions from India


Departments of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

Date of Submission03-Dec-2016
Date of Acceptance06-May-2017
Date of Web Publication23-Apr-2018

Correspondence Address:
Dr. A Gupta
Departments of Medical Oncology, Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jpgm.JPGM_727_16

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 :: Abstract 


Cytogenetic anomalies involving the 3q26 chromosomal region are rare in acute myeloid leukemia (AML). There is no such description of these anomalies from the Indian sub-continent. A total of 174 AML patients were admitted to our hospital for therapy between January 2001 and January 2008. Cytogenetic studies could be done in 115 patients; which revealed three cases with 3q26 anomalies. All were males. In the first two cases, the anomaly was detected in all the metaphases. The common features seen were the presence of only mild thrombocytopenia (relatively high platelet counts when assessed against the background of AML with high blast percentages), monosomy 7, myeloperoxidase positive blasts, mild eosinophilia, and poor therapeutic response. In the third case, the chromosome 3 anomaly was present in only one metaphase. Such an anomaly has not been reported. Only the third patient responded to induction therapy but subsequently relapsed after being in complete remission for 15 months. 3q26 anomalies are associated with monosomy 7, relatively higher platelet counts at diagnosis as compared with other non-3q rearranged AML's and poor prognosis. The precise mechanisms underlying leukemogenesis need to be elucidated and better treatments devised since these patients respond poorly to therapy.


Keywords: 3q26, acute myeloid leukemia, cytogenetics, inversion, translocation


How to cite this article:
Gupta A, Kumar L. 3q26 chromosomal anomalies in acute myeloid leukemia: First descriptions from India. J Postgrad Med 2018;64:109-11

How to cite this URL:
Gupta A, Kumar L. 3q26 chromosomal anomalies in acute myeloid leukemia: First descriptions from India. J Postgrad Med [serial online] 2018 [cited 2019 Nov 11];64:109-11. Available from: http://www.jpgmonline.com/text.asp?2018/64/2/109/217055





 :: Introduction Top


Chromosomal anomalies involving the 3q26 region are rare in acute myeloid leukemia (AML). Various studies have estimated their incidence to be ranging from 3% to 5%.[1] Recent studies suggest that their incidence may be close to 7%–10%.[2],[3] These anomalies are associated with normal or elevated platelet counts and very poor or no response to chemotherapy resulting in a dismal prognosis.[4],[5],[6],[7],[8],[9],[10],[11],[12] There are no descriptions of this anomaly from the Indian subcontinent.

Between January 2001 and January 2008, 174 cases of AML were treated at our hospital. Cytogenetic analysis of 115 cases was able to be performed and revealed three cases (2.7%) to be harboring the chromosome 3q26 anomaly. Institute Ethics Committee clearance was obtained before undertaking this study.


 :: Case Reports Top


Case 1

A 42-year-old male patient presented to us with a 1-year history of fatigue and progressive weakness [Table 1] and [Figure 1].
Table 1: Disease characteristics and response to therapy

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Figure 1: Case 1: Para-centric inversion – long arm of chromosome 3, monosomy 7: 45, inv(3)(q21q26), -7

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Case 2

A 15-year-old boy presented to us with 3 months history of intermittent fever, fatigue, weakness, pain in calves, and gum bleeding [Table 1] and [Figure 2]a.
Figure 2: (a) Case 2: Reciprocal translocation-short arm of chr 2 and long arm of chromosome 3, monosomy 7: 45, XY t(2,3)(p22, q26), -7. (b) Case 3: Trisomy 3, inversion of part of long arm of chromosome 3: 47 XY inv(3)(q21,26), +3

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Case 3

A 45-year-old male patient presented with 2 months history of progressive weakness, intermittent fever, and reduced appetite [Table 1] and [Figure 2]b.


 :: Discussion Top


3q21;q26 cytogenetic anomalies are characterized by morphologic abnormalities of thrombopoiesis in the bone marrow, patients present with higher platelet count at diagnosis as compared with non-3q rearranged ones and some cases can present with normal or elevated platelet counts as well. They are also associated with chromosomal 7 abnormalities (usually monosomy 7) and central diabetes insipidus. The most common anomalies are inv(3)(q21q26) and t(3;3)(q21q26).[1],[2],[3],[4]

The ins(3)(q26;q21q26) anomaly is rare. Associated chromosomal anomalies include - 7/del(7q) (most common), -5/del(5q), del(6q) and del(20q).[5],[6],[7],[8],[9],[10],[11] Aberrant expression of EVI1 gene has been reported almost exclusively in cases presenting with translocations involving band 3q26. EVI1 gene expression by retroviral vectors has been found to block the granulocyte colony-stimulating factor-induced differentiation of murine myeloid cells. ribophorin 1 (RPN1) at location 3q21 gets juxtaposed to 3q26 resulting in its activation.[9],[10],[11],[12]

The translocation t(2p; 3q) anomaly as seen in our second case is of two types. In one type the breakpoint on chromosome 2 is localized to bands 2p21-23, whereas the breakpoint for the other is localized to 2p15-21. This also results in activation of the EVI1 gene. It can exist as a sole anomaly/be associated with -7, del(5q), del(7q), t(9;22)(q34;q11) or with complex karyotypes. Features are typical of 3q26/EVI1 rearrangements as described above.[7] Aberrations involving 3q26 have been described in all AML subtypes (except AML-M3), chronic myeloid leukemia blast crisis, and myelodysplastic syndrome.[1],[4],[5]

In our study also the anomaly was not restricted to any particular subtype (our cases had AML-M2, AML-M4, and AML-M1, respectively). We also did not find organomegaly, lymphadenopathy, or central diabetes insipidus at presentation.

There was also no evidence of central diabetes insipidus - a condition that has been found to be associated with this anomaly.[10] Some series have noted a striking predilection for males while some have not.[1] Preferential involvement of women in t(3;3) has been described.[8] None of our patients harbored the t(3;3) anomaly. Leukocytosis was not pronounced. The third case had leukopenia.

The common features seen in the first two cases (all the metaphases involved) were the presence of only mild thrombocytopenia (relatively high platelet counts when assessed against the background of AML with high blast percentages), monosomy 7, myeloperoxidase positive blasts, mild eosinophilia, and poor or no response to therapy. They refused the option of allogenic transplantation. However, reports indicate that transplantation is also associated with poor results.

In the third case, the chromosome 3 anomaly was present in only one metaphase. The patient responded to induction therapy. He relapsed after having been in complete remission for 15 months. These cytogenetic features are unique and not described in the literature. The clinical behavior in the third case was typical of AML-M1, and he showed response to chemotherapy. The 3q26 anomaly detected in our third case was present in only one metaphase but appears clinically significant given the nature of the anomaly.

The precise mechanisms underlying the role of this anomaly in leukemogenesis needs to be elucidated and better treatments devised since these patients respond poorly to therapy.

Recent reports show that a substantial part of the EVI-1-positive AML cases respond to all-trans retinoic acid (ATRA) by induction of differentiation and decreased the clonogenic capacity of myeloid blasts. Most importantly, treatment of primary EVI-1-positive AML with ATRA leads to a significant reduction in leukemic engraftment. Combining ATRA with the currently used conventional chemotherapy might thus be a promising treatment strategy in a disease otherwise associated with dismal prognosis.[12]

Declaration of patient consent

The authors certify that appropriate patient consents were obtained.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 :: References Top

1.
Testoni N, Borsaru G, Martinelli G, Carboni C, Ruggeri D, Ottaviani E, et al.3q21 and 3q26 cytogenetic abnormalities in acute myeloblastic leukemia: Biological and clinical features. Haematologica 1999;84:690-4.  Back to cited text no. 1
    
2.
Nucifora G, Laricchia-Robbio L, Senyuk V. EVI1 and hematopoietic disorders: History and perspectives. Gene 2006;368:1-11.  Back to cited text no. 2
    
3.
Poppe B, Dastugue N, Vandesompele J, Cauwelier B, De Smet B, Yigit N, et al. EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements. Genes Chromosomes Cancer 2006;45:349-56.  Back to cited text no. 3
    
4.
Lahortiga I, Vázquez I, Agirre X, Larrayoz MJ, Vizmanos JL, Gozzetti A, et al. Molecular heterogeneity in AML/MDS patients with 3q21q26 rearrangements. Genes Chromosomes Cancer 2004;40:179-89.  Back to cited text no. 4
    
5.
Martinelli G, Ottaviani E, Buonamici S, Isidori A, Borsaru G, Visani G, et al. Association of 3q21q26 syndrome with different RPN1/EVI1 fusion transcripts. Haematologica 2003;88:1221-8.  Back to cited text no. 5
    
6.
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. 6
    
7.
Stevens-Kroef M, Poppe B, van Zelderen-Bhola S, van den Berg E, van der Blij-Philipsen M, Geurts van Kessel A, et al. Translocation t(2;3)(p15-23;q26-27) in myeloid malignancies: Report of 21 new cases, clinical, cytogenetic and molecular genetic features. Leukemia 2004;18:1108-14.  Back to cited text no. 7
    
8.
Pintado T, Ferro MT, San Román C, Mayayo M, Laraña JG. Clinical correlations of the 3q21;q26 cytogenetic anomaly. A leukemic or myelodysplastic syndrome with preserved or increased platelet production and lack of response to cytotoxic drug therapy. Cancer 1985;55:535-41.  Back to cited text no. 8
    
9.
Reiter E, Greinix H, Rabitsch W, Keil F, Schwarzinger I, Jaeger U, et al. Low curative potential of bone marrow transplantation for highly aggressive acute myelogenous leukemia with inversioin inv (3)(q21q26) or homologous translocation t(3;3) (q21;q26). Ann Hematol 2000;79:374-7.  Back to cited text no. 9
    
10.
Breccia M, Petti MC, Ottaviani E, Mancini M, D'Elia GM, Mecarocci S, et al. Diabetes insipidus as first manifestation of acute myeloid leukaemia with EVI-1-positive, 3q21q26 syndrome and T cell-line antigen expression: What is the EVI-1 gene role? Br J Haematol 2002;118:438-41.  Back to cited text no. 10
    
11.
Lugthart S, van Drunen E, van Norden Y, van Hoven A, Erpelinck CA, Valk PJ, et al. High EVI1 levels predict adverse outcome in acute myeloid leukemia: Prevalence of EVI1 overexpression and chromosome 3q26 abnormalities underestimated. Blood 2008;111:4329-37.  Back to cited text no. 11
    
12.
Verhagen HJ, Smit MA, Rutten A, Denkers F, Poddighe PJ, Merle PA, et al. Primary acute myeloid leukemia cells with overexpression of EVI-1 are sensitive to all-trans retinoic acid. Blood 2016;127:458-63.  Back to cited text no. 12
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

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2004 - Journal of Postgraduate Medicine
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