Retrospective Study of B Lymphoblastic Leukemia to Assess the Prevalence of TEL/AML1 in South India: A Study of 214 Cases and Review of Literature

Sandhya Devi G.; Faiq Ahmed; Manasi C. Mundada; Rachna Khera; Lavanya Nambaru; Krishnamohan Mallavarapu; Pavan Kumar Boyella; Veerandra Patil; Pallavi Suresh Laddha; Senthil J. Rajappa

doi:10.1055/s-0042-1742611

Indian Journal of Medical and Paediatric Oncology, Inhaltsverzeichnis

CC BY-NC-ND 4.0 · Indian J Med Paediatr Oncol 2025; 46(03): 259-268
DOI: 10.1055/s-0042-1742611

Original Article

Retrospective Study of B Lymphoblastic Leukemia to Assess the Prevalence of TEL/AML1 in South India: A Study of 214 Cases and Review of Literature

Authors

Sandhya Devi G.

¹Department of Laboratory Medicine, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Faiq Ahmed

¹Department of Laboratory Medicine, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Manasi C. Mundada

¹Department of Laboratory Medicine, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Rachna Khera

¹Department of Laboratory Medicine, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Lavanya Nambaru

¹Department of Laboratory Medicine, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Krishnamohan Mallavarapu

²Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Pavan Kumar Boyella

²Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Veerandra Patil

²Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Pallavi Suresh Laddha

²Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
Senthil J. Rajappa

²Department of Medical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India

Abstract

Introduction Translocation t(12;21)(p13;q22), a recurrent and an invisible chromosomal abnormality, resulting in TEL/AML1 gene fusion, associated with good prognosis, has been described to be a common abnormality, in children with B-acute lymphoblastic leukemia (B-ALL).

Objectives The initial observation of very few TEL/AML1 positive patients at this center on testing by fluorescence in situ hybridization (FISH) led to study the prevalence of the abnormality, compare with the global distribution, and evaluate clinical, pathological, molecular, and cytogenetic features in TEL/AML1 positive patients.

Materials and Methods A retrospective study of all B-ALL patients tested for TEL/AML1 gene fusion during the period January 2009 to November 2020 was undertaken. Clinicopathological, molecular, cytogenetic, treatment, and follow-up details were collected. All publications dealing with TEL/AML1 gene rearrangement were reviewed post Google and PubMed search.

Results TEL/AML1gene rearrangement was assessed by FISH in 178 patients and by reverse transcription polymerase chain reaction in 36 patients and detected as the sole abnormality in 8.4% patients with additional genetic abnormalities noted on FISH evaluation. Normal karyotype was noted in 14/18 (77.7%) of these patients and 2 had complex karyotype. Complete blood count revealed hemoglobin to range from 35 to 116 g/L (median: 74 g/L), white blood count: 1.01–110×10⁹/L (median: 7.8×10⁹/L), platelet counts: 10–115×10⁹/L (median: 42×10⁹/L), blast count in peripheral smear: 0–98% (median: 41%). Immunophenotyping demonstrated 94.4% were CD34 positive, common acute lymphoblastic leukemia associated antigen (CALLA) positive with aberrant expression of CD13, CD33, CD56, singly or in combination in 58.8%.

Conclusion TEL/AML1 fusion is rare in Indian patients with B-ALL and appears to be much rarer in our region. The detection of relevant specific abnormalities is of fundamental importance in B-ALL patients and these geographic variations can be used in defining management policies.

Keywords

TEL/AML1 - t(12;21) fluorescence in situ hybridization - acute lymphoblastic leukemia (ALL) - RT-PCR

Volltext

Referenzen

References
1 Borowitz MJ, Chan JKC, Downing JR, Le Beau MM, Arber DA. B lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J. eds. WHO Classification of Tumours of Hematopoietic and Lymphoid Tissues. 4th edition.. Lyon: IARC; 2017: 203-209
2 Naeim F, Rao PN. Acute myeloid leukemia. In: Naeim F, Rao PN, Grody WW. eds. Hematopathology Morphology, Immunophenotype, Cytogenetics, and Molecular Approaches. 1st edition. Amsterdam: Elsevier; 2008: 207-255
3 Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J 2017; 7 (06) e577
4 Zelent A, Greaves M, Enver T. Role of the TEL-AML1 fusion gene in the molecular pathogenesis of childhood acute lymphoblastic leukaemia. Oncogene 2004; 23 (24) 4275-4283
5 Zhang L, Parkhurst JB, Kern WF. et al. Chromosomal changes detected by fluorescence in situ hybridization in patients with acute lymphoblastic leukemia. Chin Med J (Engl) 2003; 116 (09) 1298-1303
6 Martínez-Ramírez A, Urioste M, Contra T. et al. Fluorescence in situ hybridization study of TEL/AML1 fusion and other abnormalities involving TEL and AML1 genes. Correlation with cytogenetic findings and prognostic value in children with acute lymphocytic leukemia. Haematologica 2001; 86 (12) 1245-1253
7 Gmidène A, Elghezal H, Sennana H. et al. ETV6-RUNX1 rearrangement in Tunisian pediatric B-Lineage acute lymphoblastic leukemia. Adv Hematol. 2009;2009:924301.
8 Al-Sweedan SA, Neglia JP, Steiner ME, Bostrom BC, Casey T, Hirsch BA. Characteristics of patients with TEL-AML1-positive acute lymphoblastic leukemia with single or multiple fusions. Pediatr Blood Cancer 2007; 48 (05) 510-514
9 Mosad E, Hamed HB, Bakry RM, Ezz-Eldin AM, Khalifa NM. Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study. J Hematol Oncol 2008; 1: 17
10 Siddiqui R, Nancy N, Naing WP. et al. Distribution of common genetic subgroups in childhood acute lymphoblastic leukemia in four developing countries. Cancer Genet Cytogenet 2010; 200 (02) 149-153
11 Iqbal Z. Molecular genetic studies on 167 pediatric ALL patients from different areas of Pakistan confirm a low frequency of the favorable prognosis fusion oncogene TEL-AML1 (t 12; 21) in underdeveloped countries of the region. Asian Pac J Cancer Prev 2014; 15 (08) 3541-3546
12 Khan A, Ayyub M, Ahmed S, Altaf CH, Malik HS. Frequency of three different gene mutations (TEL-AML1, E2A–PBX1 and MLL-AF4) in acute lymphoblastic leukaemia. Hematol Transfus Int J 2016; 2: 00045
13 Woo HY, Kim DW, Park H, Seong KW, Koo HH, Kim SH. Molecular cytogenetic analysis of gene rearrangements in childhood acute lymphoblastic leukemia. J Korean Med Sci 2005; 20 (01) 36-41
14 Chung HY, Kim KH, Jun KR. et al. [Prognostic significance of TEL/AML1 rearrangement and its additional genetic changes in Korean childhood precursor B-acute lymphoblastic leukemia]. Korean J Lab Med 2010; 30 (01) 1-8
15 Chen B, Wang YY, Shen Y. et al. Newly diagnosed acute lymphoblastic leukemia in China (I): abnormal genetic patterns in 1346 childhood and adult cases and their comparison with the reports from Western countries. Leukemia 2012; 26 (07) 1608-1616
16 Aydin C, Cetin Z, Manguoglu AE. et al. Evaluation of ETV6/RUNX1fusion and additional abnormalities involving ETV6 and/or RUNX1genes using fish technique in patients with childhood acute lymphoblastic leukemia. Indian J Hematol Blood Transfus 2016; 32 (02) 154-161
17 Zen PRG, Lima MC, Coser VM. et al. Prevalence of TEL/AML1 fusion gene in Brazilian pediatric patients with acute lymphoblastic leukemia. Cancer Genet Cytogenet 2004; 151 (01) 68-72
18 Yehuda-Gafni O, Cividalli G, Abrahmov A. et al. Fluorescence in situ hybridization analysis of the cryptic t(12;21) (p13;q22) in childhood B-lineage acute lymphoblastic leukemia. Cancer Genet Cytogenet 2002; 132 (01) 61-64
19 Sazawal S, Bhatia K, Gutierrez MI, Saxena R, Arya LS, Bhargava M. Paucity of TEL-AML 1 translocation, by multiplex RT-PCR, in B-lineage acute lymphoblastic leukemia (ALL) in Indian patients. Am J Hematol 2004; 76 (01) 80-82
20 Bhatia P, Binota J, Varma N. et al. Incidence of common chimeric fusion transcripts in B-cell acute lymphoblastic leukemia: an Indian perspective. Acta Haematol 2012; 128 (01) 17-19
21 Varma N, Naseem S, Binota J, Varma S, Malhotra P, Marwaha RK. Study of incidence of recurrent genetic translocation in adult and pediatric acute lymphoblastic leukemia (ALL) patients in north India. International Journal of Epidemiology 2015;44:i234–35.
22 Chopra A, Soni S, Verma D. et al. Prevalence of common fusion transcripts in acute lymphoblastic leukemia: a report of 304 cases. Asia Pac J Clin Oncol 2015; 11 (04) 293-298
23 Inamdar N, Kumar SA, Banavali SD, Advani S, Magrath I, Bhatia K. Comparative incidence of the rearrangements of TEL/AML1 and ALL1 genes in pediatric precursor B acute lymphoblastic leukemias in India. Int J Oncol 1998; 13 (06) 1319-1322
24 Siraj AK, Kamat S, Gutiérrez MI. et al. Frequencies of the major subgroups of precursor B-cell acute lymphoblastic leukemia in Indian children differ from the West. Leukemia 2003; 17 (06) 1192-1193
25 Pais AP, Amare Kadam PS, Raje GC. et al. RUNX1 aberrations in ETV6/RUNX1-positive and ETV6/RUNX1-negative patients: its hemato-pathological and prognostic significance in a large cohort (619 cases) of ALL. Pediatr Hematol Oncol 2008; 25 (06) 582-597
26 Kerketta LS, Baburao V, Ghosh K. Pattern of chromosome involvement in childhood hyperdiploid pre-B-cell acute lymphoblastic leukemia cases from India. Indian J Hum Genet 2014; 20 (01) 32-36
27 Magatha LS, Scott JX, Subramaniam G, Chandrasekaran T, Paul SFD, Koshy T. Cytogenetic and fluorescence in Situ hybridization (FISH) profile of paediatric acute lymphoblastic leukemia (ALL) in a University Hospital in South India. Med Princ Pract 2021; 30: 563-570
28 Mazloumi SH, Madhumathi DS, Appaji L, kumari Prasanna. Combined study of cytogenetics and fluorescence in situ hybridization (FISH) analysis in childhood acute lymphoblastic leukemia (ALL) in a tertiary cancer centre in South India. Asian Pac J Cancer Prev 2012; 13 (08) 3825-3827
29 Hill A, Short MA, Varghese C, Kusumakumary P, Kumari P, Morgan GJ. The t(12:21) is underrepresented in childhood B-lineage acute lymphoblastic leukemia in Kerala, Southern India. Haematologica 2005; 90 (03) 414-416
30 Siddaiahgari SR, Awaghad MA, Latha MS. Clinical, immunophenotype and cytogenetic profile of acute lymphoblastic leukemia in children at tertiary health care centre in India. Muller J of Medical Sciences and Research 2015; 6: 112-118
31 An International System for Human Cytogenomic Nomenclature (2016). Editors: McGowan-Jordan Simons A, Schmid M. Cytogenetic and Genome Research, Vol. 149, No.1–2, 2016.
32 Marwaha RK, Kulkarni KP. Childhood acute lymphoblastic leukemia: need of a national population based registry. Indian Pediatr 2011; 48 (10) 821
33 Gujaral S, Badrinath Y, Kumar A. et al. Immuno-phenotypic profile of acute leukemia: Critical analysis and insights gained at a tertiary care center in India. Blood 2008; 112: 4878
34 Swaminathan R, Rama R, Shanta V. Childhood cancers in Chennai, India, 1990-2001: incidence and survival. Int J Cancer 2008; 122 (11) 2607-2611
35 Arora RS, Eden TO, Kapoor G. Epidemiology of childhood cancer in India. Indian J Cancer 2009; 46 (04) 264-273
36 Tyagi BB, Manoharan N, Raina V. Childhood cancer incidence in Delhi, 1996–2000. Indian J Med Paediatr Oncol 2006; 27: 13-18
37 Ma SK, Wan TSK, Cheuk ATC. et al. Characterization of additional genetic events in childhood acute lymphoblastic leukemia with TEL/AML1 gene fusion: a molecular cytogenetics study. Leukemia 2001; 15 (09) 1442-1447
38 Yang M, Yi ES, Kim HJ, Yoo KH, Koo HH, Kim SH. Intrachromosomal amplification of chromosome 21 in Korean pediatric patients with B-cell precursor acute lymphoblastic leukemia in a single institution. Blood Res 2017; 52 (02) 100-105
39 Harrison CJ, Haas O, Harbott J. et al; Biology and Diagnosis Committee of International Berlin-Frankfürt-Münster study group. Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of the International Berlin-Frankfürt-Münster study group. Br J Haematol 2010; 151 (02) 132-142

Zusatzmaterial

Supplementary Material (PDF)