Increased Incidence of Trisomy 8 in Acute Myeloid Leukemia With Skin Infiltration (Leukemia Cutis)

Trisomy 8 acute myeloid leukemia (AML) is the commonest numerical aberration in AML. Here we present a global analysis of trisomy 8 AML using methylated DNA immunoprecipitation-sequencing (MeDIP-seq). The study is based on three diagnostic trisomy 8 AML and their parallel relapse status in addition to nine non-trisomic AML and four normal bone marrows (NBMs). In contrast to non-trisomic DNA samples, trisomy 8 AML showed a characteristic DNA methylation distribution pattern because an increase in the frequency of the hypermethylation signals in chromosome 8 was associated with an increase in the hypomethylation signals in the rest of the chromosomes. Chromosome 8 hypermethylation signals were found mainly in the CpG island (CGI) shores and interspersed repeats. Validating the most significant differentially methylated CGI ( P = 7.88 · 10–11identified in trisomy 8 AML demonstrated a specific core region within the gene body of HHEX, which was significantly correlated with HHEX expression in both diagnostic and relapse trisomy 8 AMLs. Overall, the existence of extra chromosome 8 was associated with a global impact on the DNA methylation distribution with identification of HHEX gene methylation as a potential diagnostic marker for trisomy 8 AML.

Download Full-text

The possible significance of trisomy 8 in acute myeloid leukemia

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20172464 ◽

2017 ◽

Vol 5 (6) ◽

pp. 2652 ◽

Cited By ~ 2

Author(s):

Salil N. Vaniawala ◽

Monika V. Patel ◽

Pratik D. Chavda ◽

Shivangi H. Zaveri ◽

Pankaj K. Gadhia

Keyword(s):

Acute Myeloid Leukemia ◽

Chromosomal Aberrations ◽

Myeloid Leukemia ◽

Chromosomal Abnormalities ◽

Prognostic Significance ◽

Chromosomal Translocation ◽

Banding Technique ◽

Trisomy 8 ◽

Increased Risk ◽

Acute Myeloid

Background: Acute myeloid leukemia (AML) is a heterogeneous disorder that results from a block in the differentiation of haematopoietic progenitor cells along with uncontrolled proliferation. Trisomy 8 is the most common recurring numerical chromosomal aberrations in acute myeloid leukemia (AML). It occurs either as a sole anomaly or together with other additional chromosomal aberrations. The prognostic significance of trisomy 8 in presence of other additional chromosomal abnormality depends on clonal cytogenetic changes. The patients with trisomy 8 had shorter survival with significantly increased risk with other chromosomal abnormality.Methods: Total 139 patients were screened between January 2016 to November 2016 who were suspected of AML cases. Bone marrow cultures were set up using conventional cytogenetic methods. Chromosomal preparation was made and subjected to GTG banding technique. Banded metaphases were analysed and karyotyped for further analysis.Results: Cytogenetic evaluation of karyotyped of 139 suspected AML patients showed 52 with t(8;21)(q22;q22), 36 with t(15;17)(q22;q12), and 11 with inv(16)(p13;q22). The rest 40 cases found with additional chromosomal abnormalities, of which 16 were sole trisomy 8 and 24 cases were found with other chromosomal abnormalities In addition, only one person found with t(8;21) and trisomy 8, while three person having t(15;17) with trisomy 8.Conclusions: AML is considered to be one of the most important cytogenetic prognostic determinants. Recurrent chromosomal translocation with trisomy 8 varying 1.9% for t(8;21) and 8.3% for t(15;17). In the present study trisomy 8 in AML with known favourable anomalies is very small. Therefore, it cannot be taken as a prognostic marker.

Download Full-text

Leukemia Cutis in a 32-Year-Old Male with Acute Myeloid Leukemia

Journal of Enam Medical College ◽

10.3329/jemc.v9i2.41416 ◽

2019 ◽

Vol 9 (2) ◽

pp. 133-135

Author(s):

Meher Afsun ◽

Rokon Uddin ◽

Md Abu Baker ◽

Iftekhar Ahmed

Keyword(s):

Acute Myeloid Leukemia ◽

Male Patient ◽

Myeloid Leukemia ◽

Clinical Presentation ◽

Systemic Disease ◽

Cutaneous Manifestation ◽

Cutaneous Lesions ◽

Initial Manifestation ◽

Leukemia Cutis ◽

Acute Myeloid

Leukemia cutis (LC) is a rare cutaneous manifestation of leukemia. Clinical presentation of the disease differs among patients depending on types. LC can precede, follow, occur simultaneously with, or present in the absence of the systemic leukemia. Leukemic involvement of the skin may appear as initial manifestation of recurrence or dissemination of systemic disease. Here we report a case of a 32-year-old male patient known to have acute myeloid leukemia with multiple cutaneous lesions diagnosed as LC. J Enam Med Col 2019; 9(2): 133-135

Download Full-text

Association of Leukemia Cutis With Survival in Acute Myeloid Leukemia

JAMA Dermatology ◽

10.1001/jamadermatol.2019.0052 ◽

2019 ◽

Vol 155 (7) ◽

pp. 826 ◽

Cited By ~ 4

Author(s):

Cynthia X. Wang ◽

Iskra Pusic ◽

Milan J. Anadkat

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Leukemia Cutis ◽

Acute Myeloid

Download Full-text

MicroRNA signatures associated with cytogenetics and prognosis in acute myeloid leukemia

Blood ◽

10.1182/blood-2007-07-098749 ◽

2008 ◽

Vol 111 (6) ◽

pp. 3183-3189 ◽

Cited By ~ 446

Author(s):

Ramiro Garzon ◽

Stefano Volinia ◽

Chang-Gong Liu ◽

Cecilia Fernandez-Cymering ◽

Tiziana Palumbo ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Mirna Expression ◽

Myeloid Leukemia ◽

Cox Regression ◽

Independent Set ◽

Microarray Platform ◽

Small Subset ◽

Trisomy 8 ◽

Molecular Abnormalities ◽

Acute Myeloid

Abstract MicroRNAs (miRNAs) are small RNAs of 19 to 25 nucleotides that are negative regulators of gene expression. To determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in acute myeloid leukemia (AML), we evaluated the miRNA expression of CD34+ cells and 122 untreated adult AML cases using a microarray platform. After background subtraction and normalization using a set of housekeeping genes, data were analyzed using Significance Analysis of Microarrays. An independent set of 60 untreated AML patients was used to validate the outcome signatures using real-time polymerase chain reaction. We identified several miRNAs differentially expressed between CD34+ normal cells and the AML samples. miRNA expression was also closely associated with selected cytogenetic and molecular abnormalities, such as t(11q23), isolated trisomy 8, and FLT3-ITD mutations. Furthermore, patients with high expression of miR-191 and miR-199a had significantly worse overall and event-free survival than AML patients with low expression (overall survival: miR-191, P = .03; and miR-199a, P = .001, Cox regression). In conclusion, miRNA expression in AML is closely associated with cytogenetics and FLT3-ITD mutations. A small subset of miRNAs is correlated with survival.

Download Full-text

Trisomy 8 in pediatric acute myeloid leukemia: A NOPHO-AML study

Genes Chromosomes and Cancer ◽

10.1002/gcc.22373 ◽

2016 ◽

Vol 55 (9) ◽

pp. 719-726 ◽

Cited By ~ 3

Author(s):

Anne Cathrine Lund Laursen ◽

Julie Damgaard Sandahl ◽

Eigil Kjeldsen ◽

Jonas Abrahamsson ◽

Peter Asdahl ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Trisomy 8 ◽

Pediatric Acute Myeloid Leukemia ◽

Acute Myeloid

Download Full-text

Trisomy 8 in the Light of Recent Cytogenetic Classification Advances. A Study From the French Acute Myeloid Leukemia Intergroup.

Blood ◽

10.1182/blood.v114.22.2594.2594 ◽

2009 ◽

Vol 114 (22) ◽

pp. 2594-2594 ◽

Cited By ~ 1

Author(s):

Nicolas Boissel ◽

Christine Terré ◽

Pascale Cornillet-Lefebvre ◽

Odile Maarek ◽

Eric Lippert ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Complete Remission ◽

Gene Mutation ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Prognostic Impact ◽

Trisomy 8 ◽

Factors Associated ◽

Acute Myeloid ◽

Similar Incidence

Abstract Abstract 2594 Poster Board II-570 Background: Trisomy 8 (+8) is one of the most common cytogenetical abnormality observed in acute myeloid leukemia (AML). The prognostic impact of +8 as sole aberration remains unclear and +8 may be classified either within intermediate- or high-risk subgroups. Recently, the prognostic impact of cytogenetic in AML has been refined by the identification of: 1) favorable genotypes in cytogenetically normal (CN) AML defined by the presence of either NPM1 gene mutation (NPM1m) or CEBPA gene mutation (CEBPAm) and the absence of FLT3 duplication (FLT3/ITD); 2) highly unfavorable AML with monosomal karyotype (MK). The aim of this study was to precise the prognostic impact of: 1) additional +8 in various cytogenetic risk subgroups; and 2) +8 as sole aberration when compared to different CN-AML genotypes. Patients: A total of 2087 patients with AML (AML-M3 excluded) were treated in the LAM-2001, LAM-SA-2002, ALFA-9802 and ALFA-9801 studies from the French AML Intergroup. After central review, cytogenetic analysis was considered successful in 1796 patients. Abnormalities were categorized according to the French AML Intergroup classification. All analysis (complete remission, CR; overall survival, OS; probability of continuous complete remission, %CCR) were stratified on studies. Results: +8 was present in 171/1796 (9.5%) with a similar incidence among the different cytogenetic subgroups: 22/243 fav-risk (9.1%), 99/1121 int-risk (8.8%), and 50/432 unfav-risk (11.6%). The incidence of +8 was significantly higher in MK-AML versus non MK-AML (30/223, 13.5%, p=.04). In none of these subgroups (fav, int, unfav, and MK), the presence of +8 was associated with a significantly different outcome (CR, OS, %CCR). When compared to patients with CN-AML, the 78 patients with +8 as sole anomaly had a similar age, a lower WBC (median WBC: 5 G/L vs 11.5 G/L, p=.004), a similar incidence of FLT3/ITD (22.2% vs 23.7%, 6/27 vs 101/426, p=.99), and a lower incidence of NPM1m (23.8% vs 46.5%, 5/21 vs 187/402, p=.05). In patients with +8 as sole anomaly, prognostic factors associated with a shorter OS were age (p=.01), high WBC (p=.01), and presence of +8 in all analyzed metaphases which was found in 1/3 of patients (p=.05). In those patients, when compared to CN-AML in general, CR rate was similar (88% vs 87%, p=.99), but %CCR and OS were shorter without, however, reaching significance (5y-%CCR: 31.8% vs 45.7%, p=.18). When compared to CN-AML patients with favorable genotypes (NPM1m or CEBPAm w/o FLT3/ITD), patients with +8 as sole anomaly had now a lower CR rate (87% vs 93%, p=.13) and significantly shorter %CCR and OS (5y-%CCR: 37.4% vs 57.8%, p=.05; 5y-OS 35.6% vs 59.0%, p=.05). Conversely, the prognosis of patients with +8 as sole anomaly appeared similar to that of patients with CN-AML w/o favorable genotypes (5y-OS: 32.6%). Conclusion: We report here the largest cohort of patients with +8. Additional +8 is equally distributed among cytogenetic risk subgroups and does not impact prognosis in each of these subgroups. Patients with AML with +8 as sole anomaly have an outcome comparable to that of CN-AML without favorable genotypes, suggesting that these patients should be managed similarly. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Activating Mutations of the FMS-Like Tyrosine Kinase-3 (FLT3) At Complete Response and Relapse in Patients with Acute Myeloid Leukemia,

Blood ◽

10.1182/blood.v118.21.3557.3557 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3557-3557

Author(s):

Aziz Nazha ◽

Jorge E. Cortes ◽

Stefan Faderl ◽

Sherry Pierce ◽

Guillermo Garcia-Manero ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Tyrosine Kinase ◽

Myeloid Leukemia ◽

Normal Karyotype ◽

Complete Response ◽

Entire Group ◽

Trisomy 8 ◽

Activating Mutations ◽

Acute Myeloid

Abstract Abstract 3557 Background – Activating mutations of the transmembrane receptor tyrosine kinase, FLT3, occur in approximately 30% of patient with acute myeloid leukemia (AML) and predict for a shorter relapse-free and overall survival. There is limited data on loss or persistence of the mutated clones at the time of complete response (CR) and their recurrence at the time of relapse. Objectives and Methods – To evaluate patterns of loss and recurrence of FLT3 mutated clones in relation to response and relapse in patients with FLT3 mutated AML treated with idarubicin and cytarabine (IA) with or without sorafenib (S), vorinostat (V), or tipifarnib (T). Bone marrow samples at diagnosis, CR and relapse were examined for the presence of FLT3 mutated clones using reverse transcription polymerase chain reaction. Results – Among 361 patients with AML treated from October 2004 to March 2010 on one of the 4 induction regimens of IA, IAS, IAV, and IAT, 321 had presentation bone marrow samples tested and 72 had FLT3 mutations (including 50 with ITD and 16 D835 with 6 having both). The median age for the entire group was 53 years (range, 17–73) and for the FLT3 mutated patients 52 years (range, 17 to 73). Cytogenetics at diagnosis in FLT3 mutated patients included normal karyotype in 48 (67%) patients, chromosome 5 and 7 abnormalities in 4(6%), trisomy 8 in 4(6%), 11q abnormalities in 2 (3%), insufficient metaphases in 3(4%), and miscellaneous in 11(16%). 271 (75%) patients overall, and 64 (89%) patients with mutated FLT3 achieved CR. Among the 56 patients with presentation FLT3-ITD, 51 achieved CR. Among 13 patients with available samples at CR, none had FLT3-ITD; 8 of these patients relapsed and 5 had FLT3-ITD positive clones at relapse (2 negative and 1 not done); Among the 38 patients with no samples at CR, 17 relapsed, 8 with a FLT3-ITD clone (1 negative and 8 not done). Among the 201 patients without FLT3-ITD at diagnosis, who achieved CR, 8 patients acquired a clone with FLT3-ITD at relapse. Conclusions – FLT3-ITD mutant clones are unstable at follow-up. Relapse may occur in their absence and they may occur for the first time at relapse. Therefore, FLT3-ITD cannot be used reliably for minimal residual leukemia monitoring. Disclosures: Ravandi: Bayer Onyx: Honoraria, Research Funding.

Download Full-text

Clinical and Pathological Features and Differential Diagnosis of Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN): a Series of Cases

Blood ◽

10.1182/blood.v128.22.5183.5183 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5183-5183 ◽

Cited By ~ 1

Author(s):

Gabriela Cesarman-Maus ◽

Carmen Lome ◽

Karla Adriana Espinosa ◽

Carmen Marcela Quezada-Fiallos ◽

Silvia Rivas ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Differential Diagnosis ◽

Dendritic Cell ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Plasmacytoid Dendritic Cell ◽

Cell Neoplasm ◽

Skin Infiltration ◽

Acute Myeloid

Abstract Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a recently recognized highly aggressive malignant proliferation of plasmacytoid dendritic-cell (PDC) precursors which consistently express CD4, CD56 and CD123. Mortality is high despite transplant and the response to treatment is poor, except for preliminary results with conjugated anti-CD123. Clinically, cutaneous involvement is the most common feature with or without the presence of initial bone marrow infiltration, however patients may present with bone marrow-only disease. BPDCN is underdiagnosed, and can be confused with several entities, including acute myeloid leukemia. We describe our experience with 7 cases of BPDCN, their clinical and pathological presentation, and describe possible misdiagnosis and the antibodies that may help in corroborating BPDCN. See table for clinical characteristics at diagnosis. Diagnosis of BPDCN must take into account clinical, morphological and immunohistochemical analysis (IHC), since these tumors variably express markers that may be shared with other neoplasias including CD56 and TCL-1. When IHC is not categorical for BPDCN, the WHO recommends reporting the cases as AML of ambiguous lineage. The typical IHC includes CD4, CD43, CD45RA, CD56, CD123, TCL1, CLA and CD68. The absence of CD56 does not exclude the diagnosis. Markers shared with other hematological tumors include: CD7, CD33, CD2,CD36 and CD38 and TdT. Thus differential diagnosis should be done primarily with A) Skin infiltration by acute myeloid leukemia (myeloperoxidase +, 7- lysozyme +, CD34 +, CD117 +/-) B) Skin Infiltration by T / NK extra nodal lymphoma ( CD8 , cytotoxic cytoplasmic granules [CCG] , granzyme B, perforin, TIA1 and EBER) C) cutaneous peripheral T lymphoma ( +/- CD8, CD2 +/-, +/- CD5, CD7 +/- and variably positive CCG´s). D) Other histiocytic and dendritic cell-neoplasms may also be considered in the differential diagnosis however the histological appearance is usually characteristic. BPDCN is a poorly known entity that should be suspected by both clinician and pathologist in order to make a correct diagnosis. Table Table. Disclosures No relevant conflicts of interest to declare.

Download Full-text