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transformation of acute lymphoid leukemia to acute myeloid leukemia

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https://www.readbyqxmd.com/read/30078796/-fgfr1-mutated-b-cell-acute-lymphoblastic-leukemia-transforming-to-myelodysplastic-myeloproliferative-neoplasm-and-acute-myeloid-leukemia
#1
Shiro Ide, Shin Ohara, Morihiro Inoue, Jian Hua, Masao Hagihara
A 77-year-old male with hyperleukocytosis and thrombocytopenia was diagnosed with Philadelphia chromosome (Ph) -negative B-cell acute lymphoblastic leukemia (ALL) ; he was treated with induction chemotherapy. Despite an initial complete remission, hyperleukocytosis was returned 18 months later. A bone marrow smear revealed a substantial increase in the number of myeloid cells with each stage of differentiation, which was markedly different from the initial presentation, resulting in the diagnosis of Ph-negative myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN)...
2018: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/30076175/transcriptional-activation-of-the-mir-17-92-cluster-is-involved-in-the-growth-promoting-effects-of-myb-in-human-ph-positive-leukemia-cells
#2
Manuela Spagnuolo, Giulia Regazzo, Marco De Dominici, Andrea Sacconi, Andrea Pelosi, Etleva Korita, Francesco Marchesi, Francesco Pisani, Alessandra Magenta, Valentina Lulli, Iole Cordone, Andrea Mengarelli, Sabrina Strano, Giovanni Blandino, Maria G Rizzo, Bruno Calabretta
MicroRNAs, non-coding regulators of gene expression, are likely to function as important downstream effectors of many transcription factors including MYB. Optimal levels of MYB are required for transformation/maintenance of BCR-ABL1-expressing cells. We investigated whether MYB silencing modulates microRNAs expression in Philadelphia-positive leukemia cells and if MYB-regulated microRNAs are important for the MYB addiction of these cells. 35 microRNAs were modulated by MYB silencing in chronic lymphoid and erythro-myeloid blast crisis BV173 and K562 leukemia cells; 15 of these were concordantly modulated in both lines...
August 3, 2018: Haematologica
https://www.readbyqxmd.com/read/29729583/shifting-of-erythroleukemia-to-myelodysplastic-syndrome-according-to-the-revised-who-classification-biologic-and-cytogenetic-features-of-shifted-erythroleukemia
#3
Sohee Ryu, Hee Sue Park, Sung-Min Kim, Kyongok Im, Jung-Ah Kim, Sang Mee Hwang, Sung-Soo Yoon, Dong Soon Lee
The 2016 revision of the World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues was published. According to 2016 WHO criteria, diagnostic criteria of acute erythroid leukemia was revised. We reassessed 34 de novo acute erythroid leukemia (AEL) diagnosed by 2008 WHO criteria, according to 2016 WHO criteria. A total of 623 patients (excluding M3) with acute myeloid leukemia including 34 patients with AEL were enrolled. Among 34 patients diagnosed with AEL, diagnosis was shifted to MDS-EB in 28 patients (28/34, 82...
April 30, 2018: Leukemia Research
https://www.readbyqxmd.com/read/29486661/clinical-outcomes-of-myeloid-lymphoid-neoplasms-with-fibroblast-growth-factor-receptor-1-fgfr1-rearrangement
#4
Kento Umino, Shin-Ichiro Fujiwara, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Daisuke Minakata, Hirofumi Nakano, Ryoko Yamasaki, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Kazuya Sato, Iekuni Oh, Ken Ohmine, Kazuo Muroi, Yoshinobu Kanda
OBJECTIVE: Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. METHODS: We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient...
February 28, 2018: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29484447/enhancer-dna-methylation-in-acute-myeloid-leukemia-and-myelodysplastic-syndromes
#5
REVIEW
Leonidas Benetatos, George Vartholomatos
DNA methylation (CpG methylation) exerts an important role in normal differentiation and proliferation of hematopoietic stem cells and their differentiated progeny, while it has also the ability to regulate myeloid versus lymphoid fate. Mutations of the epigenetic machinery are observed in hematological malignancies including acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) resulting in hyper- or hypo-methylation affecting several different pathways. Enhancers are cis-regulatory elements which promote transcription activation and are characterized by histone marks including H3K27ac and H3K4me1/2...
June 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29477370/the-bmp-pathway-a-unique-tool-to-decode-the-origin-and-progression-of-leukemia
#6
REVIEW
Florence Zylbersztejn, Mario Flores-Violante, Thibault Voeltzel, Franck-Emmanuel Nicolini, Sylvain Lefort, Véronique Maguer-Satta
The microenvironment (niche) governs the fate of stem cells (SCs) by balancing self-renewal and differentiation. Increasing evidence indicates that the tumor niche plays an active role in cancer, but its important properties for tumor initiation progression and resistance remain to be identified. Clinical data show that leukemic stem cell (LSC) survival is responsible for disease persistence and drug resistance, probably due to their sustained interactions with the tumor niche. Bone morphogenetic protein (BMP) signaling is a key pathway controlling stem cells and their niche...
May 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29175473/mechanisms-underlying-the-heterogeneity-of-myelodysplastic-syndromes
#7
REVIEW
Charles Dussiau, Michaela Fontenay
Myelodysplastic syndromes (MDS) are hematopoietic stem cell (HSC) disorders in which recurrent chromosome abnormalities and gene mutations define a clonal hematopoiesis. The MDS-initiating cell is a rare HSC which transmits the genetic abnormalities to its myeloid and lymphoid progeny. The heterogeneity of MDS phenotypes could be linked to the diversity of genetic events involving epigenetic regulators, chromatin modifiers, splicing factors, transcription factors and signaling adaptors, the various combinations and order of mutations in cooperating genes, and the variegation of clonal hematopoietic hierarchy...
February 2018: Experimental Hematology
https://www.readbyqxmd.com/read/29038614/dna-methylation-events-as-markers-for-diagnosis-and-management-of-acute-myeloid-leukemia-and-myelodysplastic-syndrome
#8
REVIEW
Geórgia Muccillo Dexheimer, Jayse Alves, Laura Reckziegel, Gabrielle Lazzaretti, Ana Lucia Abujamra
During the onset and progression of hematological malignancies, many changes occur in cellular epigenome, such as hypo- or hypermethylation of CpG islands in promoter regions. DNA methylation is an epigenetic modification that regulates gene expression and is a key event for tumorigenesis. The continuous search for biomarkers that signal early disease, indicate prognosis, and act as therapeutic targets has led to studies investigating the role of DNA in cancer onset and progression. This review focuses on DNA methylation changes as potential biomarkers for diagnosis, prognosis, response to treatment, and early toxicity in acute myeloid leukemia and myelodysplastic syndrome...
2017: Disease Markers
https://www.readbyqxmd.com/read/28655536/b-cell-identity-as-a-metabolic-barrier-against-malignant-transformation
#9
REVIEW
Lai N Chan, Markus Müschen
B-lineage and myeloid leukemia cells are often transformed by the same oncogenes, but have different biological and clinical characteristics. Although B-lineage acute lymphoblastic leukemia (B-ALL) cells are characterized by a state of chronic energy deficit, myeloid leukemia cells show abundant energy reserve. Interestingly, fasting has been demonstrated to inhibit selectively the development of B-ALL but not myeloid leukemia, further suggesting that lineage identity may be linked to divergent metabolic states in hematopoietic malignancies...
September 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28637661/the-full-transforming-capacity-of-mll-af4-is-interlinked-with-lymphoid-lineage-commitment
#10
Shan Lin, Roger T Luo, Mahesh Shrestha, Michael J Thirman, James C Mulloy
Chromosome rearrangements involving the mixed-lineage leukemia gene (MLL) create MLL-fusion proteins, which could drive both acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). The lineage decision of MLL-fusion leukemia is influenced by the fusion partner and microenvironment. To investigate the interplay of fusion proteins and microenvironment in lineage choice, we transplanted human hematopoietic stem and progenitor cells (HSPCs) expressing MLL-AF9 or MLL-Af4 into immunodeficient NSGS mice, which strongly promote myeloid development...
August 17, 2017: Blood
https://www.readbyqxmd.com/read/28609655/mll2-not-mll1-plays-a-major-role-in-sustaining-mll-rearranged-acute-myeloid-leukemia
#11
Yufei Chen, Konstantinos Anastassiadis, Andrea Kranz, A Francis Stewart, Kathrin Arndt, Claudia Waskow, Akihiko Yokoyama, Kenneth Jones, Tobias Neff, Yoo Lee, Patricia Ernst
The MLL1 histone methyltransferase gene undergoes many distinct chromosomal rearrangements to yield poor-prognosis leukemia. The remaining wild-type allele is most commonly, but not always, retained. To what extent the wild-type allele contributes to leukemogenesis is unclear. Here we show, using rigorous, independent animal models, that endogenous MLL1 is dispensable for MLL-rearranged leukemia. Potential redundancy was addressed by co-deleting the closest paralog, Mll2. Surprisingly, Mll2 deletion alone had a significant impact on survival of MLL-AF9-transformed cells, and additional Mll1 loss further reduced viability and proliferation...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28401180/uncovering-a-new-cellular-origin-for-acute-myeloid-leukemia-with-lineage-plasticity
#12
REVIEW
Melinda Czeh, Frank Rosenbauer
Although acute myeloid leukaemia (AML) is assumed to be driven by transformed haematopoietic stem and progenitor cells, we have described recently a new pathway leading to AML from T-cell progenitors. Furthermore, we could identify a subgroup of human AML with gene expression profile suggesting T-lymphoid origin and potentially novel treatment.
2017: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27913602/clonal-conversion-of-b-lymphoid-leukemia-reveals-cross-lineage-transfer-of-malignant-states
#13
Rajesh Somasundaram, Josefine Åhsberg, Kazuki Okuyama, Jonas Ungerbäck, Henrik Lilljebjörn, Thoas Fioretos, Tobias Strid, Mikael Sigvardsson
Even though leukemia is considered to be confined to one specific hematopoietic cell type, cases of acute leukemia of ambiguous lineage and patients relapsing in phenotypically altered disease suggest that a malignant state may be transferred between lineages. Because B-cell leukemia is associated with mutations in transcription factors of importance for stable preservation of lineage identity, we here investigated the potential lineage plasticity of leukemic cells. We report that primary pro-B leukemia cells from mice carrying heterozygous mutations in either or both the Pax5 and Ebf1 genes, commonly mutated in human leukemia, can be converted into T lineage leukemia cells...
November 15, 2016: Genes & Development
https://www.readbyqxmd.com/read/27859216/cooperation-of-mll-af10-om-lz-with-ptpn11-activating-mutation-induced-monocytic-leukemia-with-a-shorter-latency-in-a-mouse-bone-marrow-transplantation-model
#14
Jen-Fen Fu, Sung-Tzu Liang, Ying-Jung Huang, Kung-Hao Liang, Tzung-Hai Yen, Der-Cherng Liang, Lee-Yung Shih
PTPN11 mutation, a RAS signaling pathway mutation, is associated with MLL translocations in acute leukemia. A girl with MLL/AF10 AML was found to carry PTPN11(G503A) . To study the impact of PTPN11(G503A) cooperating with MLL/AF10 on leukemogenesis, we established a retroviral transduction/transplantation mouse model. Compared to the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11(wt) , the cells harboring PTPN11(G503A) were hypersensitive to GM-CSF and IL3, and more resistant to death upon treatment with daunorubicin but sensitive to cytarabine...
March 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27856460/architectural-and-functional-heterogeneity-of-hematopoietic-stem-progenitor-cells-in-non-del-5q-myelodysplastic-syndromes
#15
Virginie Chesnais, Marie-Laure Arcangeli, Caroline Delette, Alice Rousseau, Hélène Guermouche, Carine Lefevre, Sabrina Bondu, M'boyba Diop, Meyling Cheok, Nicolas Chapuis, Laurence Legros, Sophie Raynaud, Lise Willems, Didier Bouscary, Evelyne Lauret, Olivier A Bernard, Olivier Kosmider, Françoise Pflumio, Michaela Fontenay
Myelodysplastic syndromes (MDSs) are hematopoietic stem cell disorders in which recurrent mutations define clonal hematopoiesis. The origin of the phenotypic diversity of non-del(5q) MDS remains unclear. Here, we investigated the clonal architecture of the CD34+ CD38- hematopoietic stem/progenitor cell (HSPC) compartment and interrogated dominant clones for MDS-initiating cells. We found that clones mainly accumulate mutations in a linear succession with retention of a dominant subclone. The clone detected in the long-term culture-initiating cell compartment that reconstitutes short-term human hematopoiesis in xenotransplantation models is usually the dominant clone, which gives rise to the myeloid and to a lesser extent to the lymphoid lineage...
January 26, 2017: Blood
https://www.readbyqxmd.com/read/27846391/instructive-role-of-mll-fusion-proteins-revealed-by-a-model-of-t-4-11-pro-b-acute-lymphoblastic-leukemia
#16
COMMENT
Shan Lin, Roger T Luo, Anetta Ptasinska, Jon Kerry, Salam A Assi, Mark Wunderlich, Toshihiko Imamura, Joseph J Kaberlein, Ahmad Rayes, Mark J Althoff, John Anastasi, Maureen M O'Brien, Amom Ruhikanta Meetei, Thomas A Milne, Constanze Bonifer, James C Mulloy, Michael J Thirman
The t(4;11)(q21;q23) fuses mixed-lineage leukemia (MLL) to AF4, the most common MLL-fusion partner. Here we show that MLL fused to murine Af4, highly conserved with human AF4, produces high-titer retrovirus permitting efficient transduction of human CD34+ cells, thereby generating a model of t(4;11) pro-B acute lymphoblastic leukemia (ALL) that fully recapitulates the immunophenotypic and molecular aspects of the disease. MLL-Af4 induces a B ALL distinct from MLL-AF9 through differential genomic target binding of the fusion proteins leading to specific gene expression patterns...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27443289/cbf%C3%AE-smmhc-creates-aberrant-megakaryocyte-erythroid-progenitors-prone-to-leukemia-initiation-in-mice
#17
Qi Cai, Robin Jeannet, Wei-Kai Hua, Guerry J Cook, Bin Zhang, Jing Qi, Hongjun Liu, Ling Li, Ching-Cheng Chen, Guido Marcucci, Ya-Huei Kuo
Acute myeloid leukemia (AML) arises through multistep clonal evolution characterized by stepwise accumulation of successive alterations affecting the homeostasis of differentiation, proliferation, self-renewal, and survival programs. The persistence and dynamic clonal evolution of leukemia-initiating cells and preleukemic stem cells during disease progression and treatment are thought to contribute to disease relapse and poor outcome. Inv(16)(p13q22) or t(16;16)(p13.1;q22), one of the most common cytogenetic abnormalities in AML, leads to expression of a fusion protein CBFβ-SMMHC (CM) known to disrupt myeloid and lymphoid differentiation...
September 15, 2016: Blood
https://www.readbyqxmd.com/read/27406730/acute-lymphoblastic-leukemia-occurring-in-a-case-of-chronic-lymphocytic-leukemia
#18
İ C Haznedaroğlu, M C Savaş, M Benekli, N M Sayinalp, O I Özcebe, S Dündar
Chronic lymphocytic leukemia (CLL) is a disease characterized by variable clinical presentation and a prolonged course. However, a small proportion of cases may evolve to more aggressive forms. These include acute leukemic blastic crises of both myeloid and lymphoid types, prolymphocytoid transformation, lymphoma and multiple myeloma. We describe a case of B-CLL treated with chlorambucil, in whom a picture of acute lymphoblastic leukemia of pre-B type developed. The diagnosis of both forms of leukemia is well documented on the basis of morphological, cytochemical and immunological findings...
1997: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/27285855/bcl11a-expression-in-acute-phase-chronic-myeloid-leukemia
#19
Jiawei Yin, Fan Zhang, Huiquan Tao, Xiao Ma, Guangsong Su, Xiaoli Xie, Zhongjuan Xu, Yanwen Zheng, Hong Liu, Chao He, Zhengwei Jenny Mao, Zhiwei Wang, Weirong Chang, Robert Peter Gale, Depei Wu, Bin Yin
Chronic myeloid leukemia (CML) has chronic and acute phases. In chronic phase myeloid differentiation is preserved whereas in acute phase myeloid differentiation is blocked. Acute phase CML resembles acute myeloid leukemia (AML). Chronic phase CML is caused by BCR-ABL1. What additional mutation(s) cause transition to acute phase is unknown and may differ in different persons with CML. BCL11A encodes a transcription factor and is aberrantly-expressed in several haematological and solid neoplasms. We analyzed BCL11A mRNA levels in subjects with chronic and acute phase CML...
August 2016: Leukemia Research
https://www.readbyqxmd.com/read/27007052/differential-regulation-of-the-c-myc-lin28-axis-discriminates-subclasses-of-rearranged-mll-leukemia
#20
Lili Chen, Yuqing Sun, Jingya Wang, Hui Jiang, Andrew G Muntean
MLL rearrangements occur in myeloid and lymphoid leukemias and are generally associated with a poor prognosis, however this varies depending on the fusion partner. We modeled acute myeloid leukemia (AML) in mice using various MLL fusion proteins (MLL-FPs) and observed significantly different survival outcomes. To better understand the differences between these leukemias, we examined the genome wide expression profiles of leukemic cells transformed with different MLL-FPs. RNA-sequencing and pathway analysis identified the c-Myc transcriptional program as one of the top distinguishing features...
May 3, 2016: Oncotarget
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