Therapy-related CD7+ acute myeloid leukemia with trisomy 8 following acute monocytic leukemia

Indeterminate cell histiocytosis (ICH) is a rare proliferative disorder, in which the predominant cells share morphologic and immunophenotypic features from both Langerhans and non-Langerhans cell histiocytosis. We describe a 62-year-old man presenting a 2-month history of firm nodular lesions on the upper lip. Histopathology, immunohistochemical, and ultrastructural analysis showed typical findings of ICH. The patient was treated with thalidomide and almost complete regression of the lesions was reached within 7 months. Nevertheless, one month after remission, he developed an acute myeloid leukemia of the subtype monocytic leukemia (M5). The patient's condition rapidly worsened and he died due to a respiratory failure four weeks later. We present this case because apart of being rare it joins the effectiveness of thalidomide and the association with an acute monocytic leukemia. A review of the literature is made.

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EXTRAMEDULLARY INVOLVEMENT IN ACUTE MYELOID LEUKEMIA. A SINGLE CENTER TEN YEARS EXPERIENCE

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2021.030 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Luana Fianchi ◽

Martina Quattrone ◽

Marianna Criscuolo ◽

Silvia Bellesi ◽

Giulia Dragonetti ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Prognostic Significance ◽

Best Supportive Care ◽

Monocytic Leukemia ◽

Trisomy 8 ◽

Extramedullary Relapse ◽

Incidence Risk ◽

The Impact ◽

Acute Myeloid

The incidence, risk factors and prognostic significance of extramedullary involvement (EMI) in adult patients with acute myeloid leukemia have not been established yet. This study analyzed the clinical and biological characteristics, the impact on prognosis and the cumulative incidence of EMI in a monocentric retrospective study. All consecutive adult pts with a diagnosis of AML observed in our institution between January 2010 and December 2017 were included into the analysis.Overall 346 AMLs were analyzed. The incidence of EMI was 11% (38 pts). The involved sites were: skin (66%), CNS (23%), pleura (7%), lymph nodes (5%), peritoneum (2%), spleen (2%), pancreas (2%), breasts (2%) and bones (2%). Most pts (91%) had only one site of EMI, while 9% had multiple sites affected at the same time. Twenty-four (55%) patients showed signs of EMI at presentation, while extramedullary relapse occurred in 9 pts (24%); 5 pts had EMI both at presentation and at relapse.EMI had a significantly higher frequency in pts with monocytic and myelo-monocytic leukemia subtypes (p<0,0001), MLL rearrangements (p=0.001), trisomy 8 (p=0,02) and a specific cytofluorimetry pattern (CD117-, p= 0,03; CD56-/CD117-, p= 0,04; CD56+/CD117-, p= 0,04).An analysis regarding treatment, OS and DFS was performed only on the 28 patients who experienced EMI at the onset of their disease; one EMI patient received best supportive care and was consequently excluded from OS analysis. The other 27 patients were treated with: conventional chemotherapy (21 pts), hypomethylating agent (5 pts) and low dose citarabine (1 pts); 8 pts (28.5%) received an allogeneic stem cell transplantation (allo-HSCT). Complete remission (CR) rate after induction therapy was 22% with a median DFS of 7.4 months. Median OS of all 27 EMI pts was 11.6 months (range 2-79); this resulted significantly longer for the 8 EMI pts who undergone allo-HSCT than those (19 pts) who didn’t receive this procedure (16.7 vs 8.2 months respectively, p=0.02). Univariate and multivariate analyses showed that undergoing allo-HSCT and achieving CR were the main positive prognostic factors for survival in our population (p<0,0001).This study confirms poor prognosis for EMI pts. Allo-HSCT, applicable however only in some cases, seems to have a crucial role in the therapeutic approach of these patients, being associated with a better prognosis.

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FEATURES OF A DIFFERENTIAL DIAGNOSIS OF PEDIATRIC ACUTE MONOCYTIC LEUKEMIA (AML-M5a) ON THE EXAMPLE OF A CLINICAL CASE

South Russian Journal of Cancer ◽

10.37748/2687-0533-2020-1-1-7 ◽

2020 ◽

Vol 1 (1) ◽

pp. 76-83

Author(s):

O. I. Kit ◽

N. K. Guskova ◽

O. N. Selyutina ◽

V. V. Dmitrieva ◽

I. A. Novikova ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Clinical Case ◽

Clinical Manifestations ◽

Underlying Disease ◽

Acute Monocytic Leukemia ◽

Monocytic Leukemia ◽

Cytochemical Study ◽

Short Period ◽

Acute Myeloid

The aim of this work was to assess the significance of investigating clinical and laboratory parameters for diagnosing acute monocytic leukemia in children on the basis of a clinical case. The article demonstrates specific features of differentiating AML M5a from other forms of acute myeloid leukemia. According to the results of hematological, morphological and cytofluorimetric studies of blood and bone marrow samples, the diagnosis of acute myeloid leukemia was established. The morphological and phenotypic characteristics of blast cells hampered the diagnosis of an AML form. However, a comprehensive analysis of the expressed CD antigens allowed acute monocytic leukemia to be identified, which diagnosis was subsequently confirmed by a cytochemical study. Thus, the clinical diagnosis was established over a short period of time. This was of importance given the rising severity of the patient’s condition requiring immediate treatment, the initial hyperleukocytosis and the development of life-threatening complications associated with leukostasis in the lungs and the central nervous system. In the presented case, the clinical manifestations of the underlying disease and the results of flow cytofluorimetry were determining factors in initiating timely specific therapy.

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Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup

Haematologica ◽

10.3324/haematol.11100 ◽

2007 ◽

Vol 92 (6) ◽

pp. 763-770 ◽

Cited By ~ 30

Author(s):

M. Schaich ◽

R. F. Schlenk ◽

H. K. Al-Ali ◽

H. Dohner ◽

A. Ganser ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Individual Patient Data ◽

Meta Analysis ◽

Patient Data ◽

Complex Karyotype ◽

Trisomy 8 ◽

Acute Myeloid

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Tritsomy 8 Acute Myeloid Leukemia Analysis Reveals New Insights of DNA Methylome with Identification of HHEX as Potential Diagnostic Marker

Biomarkers in Cancer ◽

10.4137/bic.s19614 ◽

2015 ◽

Vol 7 ◽

pp. BIC.S19614 ◽

Cited By ~ 4

Author(s):

Marwa H. Saied ◽

Jacek Marzec ◽

Sabah Khalid ◽

Paul Smith ◽

Gael Molloy ◽

...

Keyword(s):

Dna Methylation ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Diagnostic Marker ◽

Cpg Island ◽

Global Analysis ◽

Extra Chromosome ◽

Chromosome 8 ◽

Trisomy 8 ◽

Acute Myeloid

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.

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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.

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Sea-Blue Histiocytosis of Bone Marrow in a Patient with t(8;22) Acute Myeloid Leukemia

Case Reports in Oncology ◽

10.1159/000508495 ◽

2020 ◽

Vol 13 (2) ◽

pp. 849-852 ◽

Cited By ~ 1

Author(s):

Osamu Imataki ◽

Makiko Uemura

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Zinc Finger Protein ◽

Fusion Gene ◽

Monocytic Leukemia ◽

Non Hodgkin Lymphoma ◽

Old Japanese ◽

Characteristic Features ◽

Acute Myeloid

An 80-year-old Japanese male was treated with chemotherapy consisting of cyclophosphamide, doxorubicin, vincristine, and prednisolone, for non-Hodgkin lymphoma. Nine months after the chemotherapy, he was diagnosed with acute myeloid leukemia (AML) (M4) with translocation 8p11 and 22q13. The patient bone marrow indicated a remarkable degree of sea-blue histiocytosis. His disease was aggressive, and he died of the disease. Sea-blue histiocytes are macrophages harboring blue vacuoles and granular deposition, which results from the phagocytosis of dead cells and the subsequent deposition of phospholipids. AML with the t(8; 22) (p11; q13) translocation is a rare subtype of AML, which is a rare translocation with a prevalence of less than 1.0% among all AML cases. The oncogenesis of t(8; 22) (p11; q13) is caused by the fusion protein monocytic leukemia zinc finger protein (MOZ) and transcription factor p300. MOZ can be fused to various translocation targets including CBT, TIF2, and p300, corresponding to t(8; 16), inv(8), and t(8; 22), respectively. This subgroup of AML reveals the hallmarks of the disease, including monocytic arrest and erythro/hemophagocytosis by blasts. A substantial proportion of the AML M4/M5 subtype harboring MOZ as an aberrant fusion gene represents erythrophagocytosis. Although rare, t(8; 22) is very specific to the AML M4/M5 subtype and seems to represent sea-blue histiocytosis as one of the characteristic features of monocytic AML with macrophage activation. Thus, sea-blue histiocytes are considered to be one of hallmarks in monocytic AML with MOZ translocation.

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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.

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