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Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review

Lineage switches in acute leukemia occur rarely, and the underlying mechanisms are poorly understood. Herein, we report the case of an elderly patient with leukemia in which the leukemia started as B-cell acute lymphoblastic leukemia (B-ALL) and later changed to B- and T-cell mixed phenotype acute l...

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Autores principales: Takeda, Reina, Yokoyama, Kazuaki, Fukuyama, Tomofusa, Kawamata, Toyotaka, Ito, Mika, Yusa, Nozomi, Kasajima, Rika, Shimizu, Eigo, Ohno, Nobuhiro, Uchimaru, Kaoru, Yamaguchi, Rui, Imoto, Seiya, Miyano, Satoru, Tojo, Arinobu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983914/
https://www.ncbi.nlm.nih.gov/pubmed/35402256
http://dx.doi.org/10.3389/fonc.2022.799982
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author Takeda, Reina
Yokoyama, Kazuaki
Fukuyama, Tomofusa
Kawamata, Toyotaka
Ito, Mika
Yusa, Nozomi
Kasajima, Rika
Shimizu, Eigo
Ohno, Nobuhiro
Uchimaru, Kaoru
Yamaguchi, Rui
Imoto, Seiya
Miyano, Satoru
Tojo, Arinobu
author_facet Takeda, Reina
Yokoyama, Kazuaki
Fukuyama, Tomofusa
Kawamata, Toyotaka
Ito, Mika
Yusa, Nozomi
Kasajima, Rika
Shimizu, Eigo
Ohno, Nobuhiro
Uchimaru, Kaoru
Yamaguchi, Rui
Imoto, Seiya
Miyano, Satoru
Tojo, Arinobu
author_sort Takeda, Reina
collection PubMed
description Lineage switches in acute leukemia occur rarely, and the underlying mechanisms are poorly understood. Herein, we report the case of an elderly patient with leukemia in which the leukemia started as B-cell acute lymphoblastic leukemia (B-ALL) and later changed to B- and T-cell mixed phenotype acute leukemia (MPAL) and acute myeloid leukemia (AML) during consecutive induction chemotherapy treatments. A 65-year-old woman was initially diagnosed with Philadelphia chromosome-negative B-ALL primarily expressing TdT/CD34/HLA-DR; more than 20% of the blasts were positive for CD19/CD20/cytoplasmic CD79a/cytoplasmic CD22/CD13/CD71.The blasts were negative for T-lineage markers and myeloperoxidase (MPO). Induction chemotherapy with the standard regimen for B-ALL resulted in primary induction failure. After the second induction chemotherapy regimen, the blasts were found to be B/T bi-phenotypic with additional expression of cytoplasmic CD3. A single course of clofarabine (the fourth induction chemotherapy regimen) dramatically reduced lymphoid marker levels. However, the myeloid markers (e.g., MPO) eventually showed positivity and the leukemia completely changed its lineage to AML. Despite subsequent intensive chemotherapy regimens designed for AML, the patient’s leukemia was uncontrollable and a new monoblastic population emerged. The patient died approximately 8 months after the initial diagnosis without experiencing stable remission. Several cytogenetic and genetic features were commonly identified in the initial diagnostic B-ALL and in the following AML, suggesting that this case should be classified as lineage switching leukemia rather than multiple simultaneous cancers (i.e., de novo B-ALL and de novo AML, or primary B-ALL and therapy-related myeloid neoplasm). A complex karyotype was persistently observed with a hemi-allelic loss of chromosome 17 (the location of the TP53 tumor suppressor gene). As the leukemia progressed, the karyotype became more complex, with the additional abnormalities. Sequential target sequencing revealed an increased variant allele frequency of TP53 mutation. Fluorescent in situ hybridization (FISH) revealed an increased number of mixed-lineage leukemia (MLL) genes, both before and after lineage conversion. In contrast, FISH revealed negativity for MLL rearrangements, which are well-known abnormalities associated with lineage switching leukemia and MPAL. To our best knowledge, this is the first reported case of acute leukemia presenting with lineage ambiguity and MLL gene amplification.
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spelling pubmed-89839142022-04-07 Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review Takeda, Reina Yokoyama, Kazuaki Fukuyama, Tomofusa Kawamata, Toyotaka Ito, Mika Yusa, Nozomi Kasajima, Rika Shimizu, Eigo Ohno, Nobuhiro Uchimaru, Kaoru Yamaguchi, Rui Imoto, Seiya Miyano, Satoru Tojo, Arinobu Front Oncol Oncology Lineage switches in acute leukemia occur rarely, and the underlying mechanisms are poorly understood. Herein, we report the case of an elderly patient with leukemia in which the leukemia started as B-cell acute lymphoblastic leukemia (B-ALL) and later changed to B- and T-cell mixed phenotype acute leukemia (MPAL) and acute myeloid leukemia (AML) during consecutive induction chemotherapy treatments. A 65-year-old woman was initially diagnosed with Philadelphia chromosome-negative B-ALL primarily expressing TdT/CD34/HLA-DR; more than 20% of the blasts were positive for CD19/CD20/cytoplasmic CD79a/cytoplasmic CD22/CD13/CD71.The blasts were negative for T-lineage markers and myeloperoxidase (MPO). Induction chemotherapy with the standard regimen for B-ALL resulted in primary induction failure. After the second induction chemotherapy regimen, the blasts were found to be B/T bi-phenotypic with additional expression of cytoplasmic CD3. A single course of clofarabine (the fourth induction chemotherapy regimen) dramatically reduced lymphoid marker levels. However, the myeloid markers (e.g., MPO) eventually showed positivity and the leukemia completely changed its lineage to AML. Despite subsequent intensive chemotherapy regimens designed for AML, the patient’s leukemia was uncontrollable and a new monoblastic population emerged. The patient died approximately 8 months after the initial diagnosis without experiencing stable remission. Several cytogenetic and genetic features were commonly identified in the initial diagnostic B-ALL and in the following AML, suggesting that this case should be classified as lineage switching leukemia rather than multiple simultaneous cancers (i.e., de novo B-ALL and de novo AML, or primary B-ALL and therapy-related myeloid neoplasm). A complex karyotype was persistently observed with a hemi-allelic loss of chromosome 17 (the location of the TP53 tumor suppressor gene). As the leukemia progressed, the karyotype became more complex, with the additional abnormalities. Sequential target sequencing revealed an increased variant allele frequency of TP53 mutation. Fluorescent in situ hybridization (FISH) revealed an increased number of mixed-lineage leukemia (MLL) genes, both before and after lineage conversion. In contrast, FISH revealed negativity for MLL rearrangements, which are well-known abnormalities associated with lineage switching leukemia and MPAL. To our best knowledge, this is the first reported case of acute leukemia presenting with lineage ambiguity and MLL gene amplification. Frontiers Media S.A. 2022-03-23 /pmc/articles/PMC8983914/ /pubmed/35402256 http://dx.doi.org/10.3389/fonc.2022.799982 Text en Copyright © 2022 Takeda, Yokoyama, Fukuyama, Kawamata, Ito, Yusa, Kasajima, Shimizu, Ohno, Uchimaru, Yamaguchi, Imoto, Miyano and Tojo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Takeda, Reina
Yokoyama, Kazuaki
Fukuyama, Tomofusa
Kawamata, Toyotaka
Ito, Mika
Yusa, Nozomi
Kasajima, Rika
Shimizu, Eigo
Ohno, Nobuhiro
Uchimaru, Kaoru
Yamaguchi, Rui
Imoto, Seiya
Miyano, Satoru
Tojo, Arinobu
Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review
title Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review
title_full Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review
title_fullStr Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review
title_full_unstemmed Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review
title_short Repeated Lineage Switches in an Elderly Case of Refractory B-Cell Acute Lymphoblastic Leukemia With MLL Gene Amplification: A Case Report and Literature Review
title_sort repeated lineage switches in an elderly case of refractory b-cell acute lymphoblastic leukemia with mll gene amplification: a case report and literature review
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983914/
https://www.ncbi.nlm.nih.gov/pubmed/35402256
http://dx.doi.org/10.3389/fonc.2022.799982
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