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Year : 2018  |  Volume : 64  |  Issue : 2  |  Page : 77-79

Acute myeloid leukemia with 3q26 abnormality: An editorial perspective

Stem Cell Laboratory, Surat Raktadan Kendra and Research Centre, Surat, Gujarat, India

Date of Web Publication23-Apr-2018

Correspondence Address:
Prof. K Ghosh
Stem Cell Laboratory, Surat Raktadan Kendra and Research Centre, Surat, Gujarat
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpgm.JPGM_255_17

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How to cite this article:
Ghosh K. Acute myeloid leukemia with 3q26 abnormality: An editorial perspective. J Postgrad Med 2018;64:77-9

How to cite this URL:
Ghosh K. Acute myeloid leukemia with 3q26 abnormality: An editorial perspective. J Postgrad Med [serial online] 2018 [cited 2023 Jun 8];64:77-9. Available from:

Acute myeloid leukemia (AML) is a difficult disease to treat. However, the advent of extensive immunophenotyping, cytogenetics, molecular genetics profiling combining with morphology, and past experiences with how the disease behaves therapeutically in adults, in pediatric age group, as AML secondary to chemoradiotherapy, AML arising out of myelodysplastic syndrome (MDS), and AML-like features as an accelerated or blastic phase of other myeloproliferative disorders allows one to classify the disorder as (i) curable with current chemotherapy therapy (ii) incurable with current chemotherapy but allogenic hemopoietic stem cell transplantation has good chance of curing them with acceptable toxicity and side effects (iii) allogenic stem cell transplant can cure with higher levels of morbidity and mortality (iv) various types of targeted therapy toward identified molecular targets of the disease (e.g. genetic, epigenetic, or at mRNA or protein level of the cell) alone or in combination with chemotherapy (v) monoclonal antibodies directed toward some of the expressed antigens on leukemic cells in various combinations (vi) none of the above therapy works, so we have to evolve experimental therapy based on the understanding of the molecular pathology of the condition. AML with pathology of 3q26 chromosomal abnormality is one such subset of AML which is difficult to treat because the remission is short lasting spanning only few months.[1] In the current issue of the journal, three cases with this pathology have been reported.[2] The authors could get only three such cases out of 115 analyzed with karyotype over 8-year period, giving a prevalence of 2.6% which agrees well with the current literature.[1] Two of the patients had this abnormality in all the chromosome plates examined, and one of the patients showed this abnormality in only one of the cells.

In all the three patients, there was loss of chromosome 7 which is also well known with this type of cytogenetic pathology, and all the patients had resistant disease though none had diabetes insipidus. This was unusual but not unheard of as 66% of patients with this pathology show diabetes insipidus. The very fact that in one patient only one cell showed the cytogenetic changes of the disease proves that this change itself is not constitutional and cannot explain similar changes in adenohypophysis explaining diabetes insipidus.

However, this disease has been reported in mother and daughter from the same family.[3] Moreover, this pathology has also been reported from across the world,[1],[3],[4],[5] though from this country, this is an early report.

This cytogenetic pathology was initially detected way back in 1985 by French workers in chronic myeloid leukemia (CML) patients who were undergoing blastic transformation.[5] Subsequently, for a few years, this abnormality continued to be detected in CML and other myeloproliferative disorders when the aggressive phase of the disease was unfolding. Subsequently, the patients with MDS and AML were also found to be associated with similar chromosomal abnormality and clinically these patients presented with relatively high platelet count (10%–15%), patients with 3q26 abnormality were found to have platelet counts above 500 × 109/L, and a large number of patients presented with associated diabetes insipidus presumably of central origin irrespective of whether autopsy studies showed infiltration by leukemic cells or not. Diabetes insipidus in this condition is correctable by exogenous vasopressin and often remits with clinical remission of the disease.[1],[6]

This particular subset of AML was suspected to be a new entity [7] which has been included in 2008 WHO classification of AML; however, authorities feel that, whether MDS or AML, patients with this cytogenetic change behave uniformly poorly and should be put together as one type of disease with a spectrum of blast count and morphology.

Over the time, molecular pathology of the 3q26 translocation has been worked out. This pathology consists of t(3)(q21, q26), t(3,3)(q21, q26), Ins t3(q26), del 3q21-26. This pathology originates due to breakage of a proto-oncogene site ecotropic virus integration (EVI) in 3q26.

EVI is a protooncogene. In association with upstream MDS gene, it normally forms a MDS–EVI COM plex family. In this subset of AML, there is breakage in this area, several splice variants are produced, and EVI mRNA and EVI protein is increased in leukemic cells. Normally, this gene product has both transcription activation and transcription inhibition motif as well as epigenetic modification capacity through histone acetylation and DNA methylation through its zinc finger domain, polyproline domain, and SET domain.[6]

Some of these domains are disrupted with this pathology and they are capable of producing dysmegakaryopoiesis with micromegakaryocytes and myelodysplasia.[6],[7] However, though thrombopoietin gene is present in chromosome 3, thrombopoietin level in this condition is not increased and the cause of thrombocytosis is not known.[8]

This translocation also disturbs the transcriptional activating area of GATA2 gene which has immense role in late hemopoietic cell differentiation. Hence, this pathology of 3q26 produces a type of haploinsufficiency of GATA2 transcription factor as a part of somatic mutation and produces a partial MonoMAC syndrome.[9],[10] However, why this AML is almost always associated with del 7 or del7q is an enigma. Del 7 is not essential for the production of diabetes insipidus, but it is possible that 3q26 cells get some growth advantage when associated with del 7/7q. Other chromosomal and genetic pathologies are often associated with this type of AML [Table 1].[11]
Table 1: Distribution of karyotypes and specific chromosomal abnormalities involving 3q26 rearrangement in myeloid neoplasms

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Although diabetes insipidus in this disease remains an enigma, one of the theories of its occurrence is absorption of vasopressin by abnormal platelets and megakaryocytes.[1],[6] Presence of abnormally high serum levels of sodium (>150 mEq) along with immature immunophenotype with high proportion of CD34, CD117, human leukocyte antigen antigen DR related, and CD56 positive blast cells may alert the treating doctor of its presence, and dysmegakaryopoiesis with micromegakaryocytes will only strengthen the suspicion of 3q26 disease before karyotyping is done.

Treatment of this condition is difficult as remission is short lasting. However, studies have shown that Ras and receptor tyrosine kinase activity are upregulated in this disease,[12] and a right kind of inhibitor targeting this pathway may eventually be available. All-transretinoic acid was successfully used in the current report. Similarly, Brazilian authors have used a combination of decitabine and lenalidomide in these patients with some success.[13] Till that time, these patients should be properly counseled and should be quickly prepared for allogenic stem cell transplantation within the short window of first remission if other conditions, i.e. finance, donor, and center permit.

The authors of the present article need to be congratulated for bringing to the notice of Indian hematologists this important cytogenetic subset of AML with a syndromic presentation.

 :: References Top

Wang HY, Rashidi HH. The new clinicopathologic and molecular findings in myeloid neoplasms with inv (3)(q21q26)/t(3;3)(q21;q26.2). Arch Pathol Lab Med 2016;140:1404-10.  Back to cited text no. 1
Gupta A, Kumar L. 3q26 chromosomal anomalies in acute myeloid leukemia:First descriptions from India. J Postgrad Med 2018;64:109-11.  Back to cited text no. 2
[PUBMED]  [Full text]  
Lawrie A, Stevenson DA, Doig TN, Vickers MA, Culligan DJ. Acute myeloid leukemia presenting in a mother and daughter pair with the identical acquired karyotypic abnormality consisting of inversion 3q21q26 and monosomy 7: A review of possible mechanisms. Cancer Genet 2012;205:599-602.  Back to cited text no. 3
Chung HJ, Seo EJ, Kim KH, Jang S, Park CJ, Chi HS, et al. Hematologic and clinical features of 3q21q26 syndrome: Extremely poor prognosis and association with central diabetes insipidus. Korean J Lab Med 2007;27:133-8.  Back to cited text no. 4
Cariou R, Harousseau JL, André MJ, Talmant P, Bray B, Garand R. Chromosome 3 abnormalities with dysmegakaryocytopoiesis in in subacute transformation in chronic myeloid leukemia. Nouv Rev Fr Hematol 1985;27:23-6.  Back to cited text no. 5
Hinai AA, Valk PJ. Review: Aberrant EVI1 expression in acute myeloid leukaemia. Br J Haematol 2016;172:870-8.  Back to cited text no. 6
Lavabre-Bertrand T, Bourquard P, Chiesa J, Berthéas MF, Lefort G, Taïb J, et al. Diabetes insipidus revealing acute myelogenous leukaemia with a high platelet count, monosomy 7 and abnormalities of chromosome 3: A new entity? Eur J Haematol 2001;66:66-9.  Back to cited text no. 7
Bouscary D, Fontenay-Roupie M, Chretien S, Hardy AC, Viguié F, Picard F, et al. Thrombopoietin is not responsible for the thrombocytosis observed in patients with acute myeloid leukemias and the 3q21q26 syndrome. Br J Haematol 1995;91:425-7.  Back to cited text no. 8
Ohyashiki JH, Ohyashiki K, Shimamoto T, Kawakubo K, Fujimura T, Nakazawa S, et al. Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: Possible association with GATA-1, GATA-2, and stem cell leukemia gene expression. Blood 1995;85:3713-8.  Back to cited text no. 9
Ding LW, Ikezoe T, Tan KT, Mori M, Mayakonda A, Chien W, et al. Mutational profiling of a MonoMAC syndrome family with GATA2 deficiency. Leukemia 2017;31:244-5.  Back to cited text no. 10
De Braekeleer M, Morel F, Douet-Guilbert N, Le Bris MJ, De Braekeleer E, Basinko A, et al. 3q26/EVI1 rearrangements in myeloid hemopathies: A cytogenetic review. Future Oncol 2015;11:1675-86.  Back to cited text no. 11
Gröschel S, Sanders MA, Hoogenboezem R, Zeilemaker A, Havermans M, Erpelinck C, et al. Mutational spectrum of myeloid malignancies with inv(3)/t(3;3) reveals a predominant involvement of RAS/RTK signaling pathways. Blood 2015;125:133-9.  Back to cited text no. 12
Todaro J, Bollmann PW, Rother ET, del Giglio A. Azacitidine and lenalidomide as an alternative treatment for refractory acute myeloid leukemia: A case report. Sao Paulo Med J 2015;133:271-4.  Back to cited text no. 13


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