Loading

Journal of Hematology and Transfusion

Identification of Atypical Pml or Rara Fusion Transcript by Molecular, Cytogenetics and Flow Cytometry Analysis: A Case Report

Case Report | Open Access

  • 1. Hematology and Transplantation CSE, Cardarelli Hospital, Italy
  • 2. Molecular Biology Laboratory, Hematology and Transplantation CSE, Cardarelli Hospital, Italy
  • 3. Unit of Transfusional Medicine, Cardarelli Hospital, Italy
  • 4. Molecular Biology and Clinical Genetic Unit, Cardarelli Hospital, Italy
  • 5. Department of Molecular Medicine and Biotechnology, University Federico II
  • 6. Ceinge- Advanced Biotechnologies Center, Italy
  • 7. Stem Cell Transplant Program, AORN Cardarelli, Naples
  • 8. Department of Biomedicine and Preventive, Tor Vergata University, Italy
+ Show More - Show Less
Corresponding Authors
Assunta Viola, Molecular Biology Laboratory, Hematology and Transplantation CSE, Cardarelli Hospital, Naples, Italy, Tel: 3384792316
Abstract

Acute Promyelocytic Leukemia (APL) is characterized by the PML-RARA fusion gene, as a consequence of the t (15;17(q22;q21) translocation. Depending on the PML breakpoint, usually located within intron6, exon6, or intron 3, different PML/RARA transcript isoforms may be generated: long (bcr1), variant (bcr2), and short (bcr3), respectively. We report the characterization of a case of APL with atypical PML/RARA transcript, which was not clearly detectable using standard molecular procedure. Differential detection of PML-RARA bcr1, bcr2, bcr3 fusion transcripts were analyzed using a LAMP technology based kit (DiaSorin Molecular) and no amplification detected. Subsequently a Real time PCR performed using HemaVision-28Q kit (DNA Diagnostic), no detecting amplification. Given the strong clinical and morphological suspicion, we tested the sample for RT-PCR (Biomed protocol) using PML-A2 and RARA-B primers. Analysis of PCR product showed one specific band of 440 bp, a size that does not correspond with the recognized size of the typical transcripts.

The immunophenotipic characterization carried out on FACS CANTO II BD, showed 90 % of abnormal mononuclear cells 45% of which expressed CD34 and a myeloid phenotype (positive for CD117, CD13, CD33 and partial for CD2 and MPO). Apart from this population with the help of logical gate, we found a population that did not express CD34 and HLA DR and had cytometric characteristics of APL.

Analysis of the bone marrow (BM) aspirate demonstrated a markedly hypercellular marrow with 40% myeloblasts and 30% abnormal promyelocytes of medium-sized, with bilobed nuclei and hypergranulated cytoplasm and rare Auer bodies. The traditional cytogenetic analysis at the diagnosis, assayed by the R- banding, revealed the following karyotype: 46, XY, t(15;16;17) (q24;p13;q21) [18]/47, XY, +8, t(15;16;17) (q24;p13;q21)[2].

In this report, we describe a patient with this specific translocation involving three chromosomes: 15, 17 and 16.

Keywords

APL, atypical PML/RARA , Real Time PCR

ABBREVIATIONS

APL: Acute Promyelocytic Leukemia

Cite this article

Viola A, Muggianu SM, Peluso R, Caputo M, Pisa M, et al. (2022) Identification of Atypical Pml/Rara Fusion Transcript by Molecular, Cytogenetics and Flow Cytometry Analysis: A Case Report. J Hematol Transfus 9(1): 1106

INTRODUCTION

Acute Promyelocytic Leukemia (APL) is a subtype of Acute Myeloid Leukemia (AML) with specific clinical and biological features accounting for about 10 percent of cases [1].

The disease is characterized by the PML-RARA fusion gene, as a consequence of the t(15;17(q22;q21)translocation. Depending on the PML breakpoint, usually located within intron6, exon6, or intron 3, respectively, different PML/RARA transcript isoforms may be generated: long (bcr1), variant (bcr2), and short (bcr3), respectively. These fusion genes are sensitive to retinoid differentiating agents, such as all-trans retinoic acid (ATRA) and antiapoptotic agent arsenic trioxide [2].

Although t (15;17) (q22; q21) has been detected in ~90% of APL patients, variant translocations have been reported in a few APL patients; in particular, chromosomal rearrangements in addition to t (15;17) occur 25-40% of APL patients with a large preponderance of trisomy 8.

We report the characterization of a case of APL with atypical PML/RARA transcript, which was not clearly detectable using standard molecular procedure needing additional investigation for the identification of the PML-RARA fusion.

CASE PRESENTATION

A 31year old man presented at the Emergency and then to Hematology Unit of Cardarelli Hospital (Naples) in April 2021 with malaise, intermittent vomiting and an asthenia. A blood examination demonstrated a hemoglobin (Hb) count of 130 g/l, a white blood cell (WBC) count of 5.02x109/l, with 50 % atypical cells and a platelet count of 28x109/l.

Coagulation tests identified a prothrombin time of 1.82, a normal prothrombin international ratio of 0.86, a fibrinogen level of 100 mg/l and a D-dimer of 2955 ng/ml. Analysis of the bone marrow (BM) aspirate demonstrated a markedly hypercellular marrow with 40% blasts, characterized by medium to large cells with altered nucleus/ cytoplasm ratio, and 30% abnormal promyelocytes, of medium-sized, with bilobed nuclei and hyper granulated cytoplasm and rare Auer bodies (Figure 1).

Bone marrow showing massive infiltration of typical cells with APL classic morphology.

Figure 1 Bone marrow showing massive infiltration of typical cells with APL classic morphology

The immunophenotipic characterization carried out on FACS CANTO II BD, showed 90 % of abnormal mononuclear cells 45% of which expressed CD34 and a myeloid phenotype (positive for CD117, CD13, CD33 and partial for CD2 and MPO). Apart from this population with the help of logical gate, we found a population that did not express CD34 and HLA DR and had cytometric characteristics of APL (Figure 2).

Two pathological cell populations observed in the examined bone marrow aspirate sample, which in the CD45 vs SSC dot-plot are located in area 4 vs 3: 45% population expresses the following phenotype: CD34+ CD13+ CD117±CD2± HLA DR- MPO+; 35% population expresses the following phenotype: CD34- CD13+ CD117± CD33+ CD2± HLA DR- MPO+

Figure 2 Two pathological cell populations observed in the examined bone marrow aspirate sample, which in the CD45 vs SSC dot-plot are located in area 4 vs 3:

45% population expresses the following phenotype: CD34+ CD13+ CD117±CD2± HLA DR- MPO+;

35% population expresses the following phenotype: CD34- CD13+ CD117± CD33+ CD2± HLA DR- MPO+

Reverse transcriptase-polymerase chain reaction (RT-PCR) performed differential detection of PML-RARA bcr1, bcr2, bcr3 fusion transcripts were analyzed using a LAMP technologybased kit (Dia Sorin Molecular) and no amplification detected. Subsequently a Real Time PCR performed using HemaVision28Q kit (DNA Diagnostic), no detecting amplification. Given the strong clinical and morphological suspicion, we tested the sample for RT-PCR (Biomed protocol) using PML-A2 and RARA-B primers and PML-A1 and RARA B. Analysis of PCR product using first two primers showed one specific band of 440 bp, a size that does not correspond with the recognized size of the typical bcr3 transcripts (Figure 3A), while using the other primers that identify bcr-1 transcript no amplification was detected (Figure 3B).

A/B: Gel-electrophoresis of patient sample at diagnosis using conventional RT-PCR condition for bcr-3 (A) and bcr-1 (B) amplification. Lane 1-2 UPN 129 indicate patient samples; lane 3 NTC, non-template control, lane 4 PC positive control; and lane 5 e 6 respectively DNA ladder Marker V 8-857 bp Roche Diagnostics Germany and Marker VI 154-2176 bp Roche Diagnostics Germany

Figure 3 A/B: Gel-electrophoresis of patient sample at diagnosis using conventional RT-PCR condition for bcr-3 (A) and bcr-1 (B) amplification. Lane 1-2 UPN 129 indicate patient samples; lane 3 NTC, non-template control, lane 4 PC positive control; and lane 5 e 6 respectively DNA ladder Marker V 8-857 bp Roche Diagnostics Germany and Marker VI 154-2176 bp Roche Diagnostics Germany.

The traditional cytogenetic analysis at the diagnosis, assayed by the R- banding, revealed the following karyotype: 46, XY, t(15;16;17) (q24;p13;q21)[18]/47,XY,+8,t(15;16;17) (q24;p13;q21) (Figure 4).

 Banded karyotype showing 46, XY, t(15;16;17)(q24;p13;q21)(panelA) and 47, XY, +8, t(15;16;17)(q24;p13;q21) (panel B).

Figure 4 Banded karyotype showing 46, XY, t(15;16;17)(q24;p13;q21)(panelA) and 47, XY, +8, t(15;16;17)(q24;p13;q21) (panel B).

This report describes a patient with this specific translocation involving three chromosome: 15, 17 and 16. Another studies reported a case with the coexistence of t(15;17) and complex variant t(15;16;17)(q22;q24;q21) [3]. In order to get a correct identification of transcript so to perform sensitive and specific quantitative evaluation of MDR during the follow up we carried out direct sequencing of PCR product.

The patient was diagnosed as APL according to the results of bone marrow morphology, cytogenetics, and molecular biology, with a rare PML RARA point of fusion. The patient was started on all-trans retinoic acid (ATRA) at 45?mg/m2 orally on days 1 to 28 (4 tablets h 7.00 am and pm / daily), arsenic trioxide (ATO) (10 mg ev / daily) intravenously on days 3 to 28 (from day +8 until day+17 he underwent a reduction to half a dose because of ponderal increase). At the same time, frequent plasma and blood transfusion, infection control, and other symptomatic support treatment given to the patient. On May 19, 2021, he was discharged at home; the blood routine showed a leukocyte count of 3.37?×?109 /L N 51 %, a hemoglobin level of 10.1 g / dl, and a platelet count of 261?×?109 /L. Subsequently he underwent consolidation therapy (ATRA+ATO) for three cycles, according to literature [4-6], keeping molecular complete remission. Actually, the patient is in good health conditions.

DISCUSSION

In the present report, we described a case of patient with APL characterized by novel atypical PML/RARA fusion transcript. Result of standard molecular and immunophenotipic analysis was not clear while the morphology and the clinical features were highly suggestive for APL.

In most cases the best diagnostic option for APL is RT-PCR testing; however, each testing modality has its own advantages.

Conventional karyotype can identify the usual t(15;17) and may also identify other genetic abnormalities that have prognostic significance, but requires longer response time and this is not acceptable in APL.

RT-PCR is the most sensitive test, also used for monitoring MRD as well as to identify cryptic translocation, and allows the identification of the specific translocations subtype, including bcr- 1,-2,-3.

In our case, using different molecular test such as Lamp technologies based Kit (DiaSorin Molecular) and a Real time PCR using HemaVision-28Q kit (DNA Diagnostic) no amplification detected.

Then RT-PCR for PML/RARA detection was carried out using standard protocol(Biomed) and the analysis of sample by gel – electrophoresis showed an atypical size respect classic size of the typical isoform (bcr1,bcr2,bcr3).

In this case, it was necessary to carry out additional investigations for the identification of the PML-RARA isoform.

For this reason, we used the Sanger sequencing approach, a methodology used to study gene regions associated with a defined phenotype, to confirm next generation sequencing (NGS) variants, to detect minor allele fractions up to 5%, or read contiguous sequences up to 1,000 bases. Gene fragment analysis based on simple and straightforward workflows and is used in a wide range of applications, such as mutation detection, genotyping, identification of short tandem repeats, and gene expression profiling.

The methodology used in this case report confirmed the sequence identified through the cytogenetic approach; in addition, it allowed establishing that the PML-RARA fusion gene sequence had kept the reading code unchanged.

The final diagnosis made was APL and the patient started therapy with arsenic trioxide and all- trans-retinoic-acid. Nowadays he is in complete remission after 18 months after diagnosis. Actually, to the best of our knowledge, 52 cases with complex translocation have been previously reported [7-10].

The majority of previous studies observed no difference in clinical outcome between APL with typical t(15;17) and APL with complex translocations [11,12].

This case indicates that the use of different experimental approaches and different techniques is necessary to confirm the diagnosis of difficult cases of APL and is fundamental for minimal residual disease (MRD) monitoring.

REFERENCES

1. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasm and acute leukemia. Blood. 2016; 127: 2391- 2405.

2. Cecconi L, Divona M, Ciardi C, Ottone T, Ferrantini A, Lavorgna S, et al. PML-RARα Kinetics and impact of FLT3-ITD mutations in newly diagnosed acute promyelocytic leukemia treated with ATRA and ATO or ATRA and chemotherapy. Leukemia. 2016; 10: 1987-1992.

3. Zhang Rui, Young-Mi Kim, Xianfu Wang, Yan Li, Hui Pang, Ji-Yun Lee, et al. Coexistence of t(15;17) and t(15;16;17) detected by fluorescence in situ hybridization in a patient with acute promyelocytic leukemia. A case report and literature review. Oncol Lett. 2014; 8: 1001-1008.

4. Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013; 369:111-121.

5. Ferrara F. Acute promyelocytic leukemia: what are the treatment options?. Expert Opin Pharmacother. 2010; 11: 587-596.

6. Cicconi L, Platzbecker U, Avvisati G, Faoloni F, Thiede C, Vignetti M, et al. Long-term results of all-trans retinoic acid and arsenic trioxide in non-high-risk acute promyelocytic leukemia: update of the APL0406 Italian- German randomized trial. Leukemia. 2020; 34: 914-918.

7. Wang Y, Ma J, Liu X, Xu L, Wang L, Cen J, et al. A complex translocation (3;17;15) in acute promyelocitic leukemia confirmed by fluorescence in situ hybridization. Oncol Lett. 2016; 12: 4717-4719.

8. Lili LV, Longfei Yang, Honghua Cui, Tonghui Ma. A complex translocation (1;17;15) with spliced short type PML-RARA fusion transcripts in acute promyelocitic leukemia: A case report. Experimental and therapeutic Medicine. 2019; 17: 1360-1366.

9. Iaccarino L, Divona M, Ottone T, Cicconi L, Lavorgna S, Ciardi C et al. Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia. Genes Chromosomes Cancer. 2019; 58: 60-65.

10.Liguori Alessandro, Ibanez Marian, Sargas Claudia, Sanz Miguel Angel, Barragan Eva, Cervera Josè. Acute Promyelocitic Leukemia: A constellation of molecular events around a single PML-RARA fusion gene. Cancers. 2020; 12: 624.

11.Wiernik PH, Sun Z, Gundacker H, Dewald G, Slovak ML, Paietta E, et al. Prognostic implication of addictional chromosome abnormalities among patients with de novo acute promyelocitic leukemia with t(15;17). Med Oncol. 2012; 29: 2095-2101.

12.Fujishima M, Takahashi N, Miura I, Kobayashi Y, Kume M, Nishinari T, et al. A PML/RARA chimeric gene on chromosome 2 in a patient with acute promyelocitic leukemia (M3) associated with a new variant traslocation: t(2;15;17)(q21;q22;q21). Cancer Genet Cytogenet. 2000; 120: 80-82.

Viola A, Muggianu SM, Peluso R, Caputo M, Pisa M, et al. (2022) Identification of Atypical Pml/Rara Fusion Transcript by Molecular, Cyto-genetics and Flow Cytometry Analysis: A Case Report. J Hematol Transfus 9(1): 1106.

Received : 30 Nov 2022
Accepted : 14 Dec 2022
Published : 15 Dec 2022
Journals
Annals of Otolaryngology and Rhinology
ISSN : 2379-948X
Launched : 2014
JSM Schizophrenia
Launched : 2016
Journal of Nausea
Launched : 2020
JSM Internal Medicine
Launched : 2016
JSM Hepatitis
Launched : 2016
JSM Oro Facial Surgeries
ISSN : 2578-3211
Launched : 2016
Journal of Human Nutrition and Food Science
ISSN : 2333-6706
Launched : 2013
JSM Regenerative Medicine and Bioengineering
ISSN : 2379-0490
Launched : 2013
JSM Spine
ISSN : 2578-3181
Launched : 2016
Archives of Palliative Care
ISSN : 2573-1165
Launched : 2016
JSM Nutritional Disorders
ISSN : 2578-3203
Launched : 2017
Annals of Neurodegenerative Disorders
ISSN : 2476-2032
Launched : 2016
Journal of Fever
ISSN : 2641-7782
Launched : 2017
JSM Bone Marrow Research
ISSN : 2578-3351
Launched : 2016
JSM Mathematics and Statistics
ISSN : 2578-3173
Launched : 2014
Journal of Autoimmunity and Research
ISSN : 2573-1173
Launched : 2014
JSM Arthritis
ISSN : 2475-9155
Launched : 2016
JSM Head and Neck Cancer-Cases and Reviews
ISSN : 2573-1610
Launched : 2016
JSM General Surgery Cases and Images
ISSN : 2573-1564
Launched : 2016
JSM Anatomy and Physiology
ISSN : 2573-1262
Launched : 2016
JSM Dental Surgery
ISSN : 2573-1548
Launched : 2016
Annals of Emergency Surgery
ISSN : 2573-1017
Launched : 2016
Annals of Mens Health and Wellness
ISSN : 2641-7707
Launched : 2017
Journal of Preventive Medicine and Health Care
ISSN : 2576-0084
Launched : 2018
Journal of Chronic Diseases and Management
ISSN : 2573-1300
Launched : 2016
Annals of Vaccines and Immunization
ISSN : 2378-9379
Launched : 2014
JSM Heart Surgery Cases and Images
ISSN : 2578-3157
Launched : 2016
Annals of Reproductive Medicine and Treatment
ISSN : 2573-1092
Launched : 2016
JSM Brain Science
ISSN : 2573-1289
Launched : 2016
JSM Biomarkers
ISSN : 2578-3815
Launched : 2014
JSM Biology
ISSN : 2475-9392
Launched : 2016
Archives of Stem Cell and Research
ISSN : 2578-3580
Launched : 2014
Annals of Clinical and Medical Microbiology
ISSN : 2578-3629
Launched : 2014
JSM Pediatric Surgery
ISSN : 2578-3149
Launched : 2017
Journal of Memory Disorder and Rehabilitation
ISSN : 2578-319X
Launched : 2016
JSM Tropical Medicine and Research
ISSN : 2578-3165
Launched : 2016
JSM Head and Face Medicine
ISSN : 2578-3793
Launched : 2016
JSM Cardiothoracic Surgery
ISSN : 2573-1297
Launched : 2016
JSM Bone and Joint Diseases
ISSN : 2578-3351
Launched : 2017
JSM Bioavailability and Bioequivalence
ISSN : 2641-7812
Launched : 2017
JSM Atherosclerosis
ISSN : 2573-1270
Launched : 2016
Journal of Genitourinary Disorders
ISSN : 2641-7790
Launched : 2017
Journal of Fractures and Sprains
ISSN : 2578-3831
Launched : 2016
Journal of Autism and Epilepsy
ISSN : 2641-7774
Launched : 2016
Annals of Marine Biology and Research
ISSN : 2573-105X
Launched : 2014
JSM Health Education & Primary Health Care
ISSN : 2578-3777
Launched : 2016
JSM Communication Disorders
ISSN : 2578-3807
Launched : 2016
Annals of Musculoskeletal Disorders
ISSN : 2578-3599
Launched : 2016
Annals of Virology and Research
ISSN : 2573-1122
Launched : 2014
JSM Renal Medicine
ISSN : 2573-1637
Launched : 2016
Journal of Muscle Health
ISSN : 2578-3823
Launched : 2016
JSM Genetics and Genomics
ISSN : 2334-1823
Launched : 2013
JSM Anxiety and Depression
ISSN : 2475-9139
Launched : 2016
Clinical Journal of Heart Diseases
ISSN : 2641-7766
Launched : 2016
Annals of Medicinal Chemistry and Research
ISSN : 2378-9336
Launched : 2014
JSM Pain and Management
ISSN : 2578-3378
Launched : 2016
JSM Women's Health
ISSN : 2578-3696
Launched : 2016
Clinical Research in HIV or AIDS
ISSN : 2374-0094
Launched : 2013
Journal of Endocrinology, Diabetes and Obesity
ISSN : 2333-6692
Launched : 2013
Journal of Substance Abuse and Alcoholism
ISSN : 2373-9363
Launched : 2013
JSM Neurosurgery and Spine
ISSN : 2373-9479
Launched : 2013
Journal of Liver and Clinical Research
ISSN : 2379-0830
Launched : 2014
Journal of Drug Design and Research
ISSN : 2379-089X
Launched : 2014
JSM Clinical Oncology and Research
ISSN : 2373-938X
Launched : 2013
JSM Bioinformatics, Genomics and Proteomics
ISSN : 2576-1102
Launched : 2014
JSM Chemistry
ISSN : 2334-1831
Launched : 2013
Journal of Trauma and Care
ISSN : 2573-1246
Launched : 2014
JSM Surgical Oncology and Research
ISSN : 2578-3688
Launched : 2016
Annals of Food Processing and Preservation
ISSN : 2573-1033
Launched : 2016
Journal of Radiology and Radiation Therapy
ISSN : 2333-7095
Launched : 2013
JSM Physical Medicine and Rehabilitation
ISSN : 2578-3572
Launched : 2016
Annals of Clinical Pathology
ISSN : 2373-9282
Launched : 2013
Annals of Cardiovascular Diseases
ISSN : 2641-7731
Launched : 2016
Journal of Behavior
ISSN : 2576-0076
Launched : 2016
Annals of Clinical and Experimental Metabolism
ISSN : 2572-2492
Launched : 2016
Clinical Research in Infectious Diseases
ISSN : 2379-0636
Launched : 2013
JSM Microbiology
ISSN : 2333-6455
Launched : 2013
Journal of Urology and Research
ISSN : 2379-951X
Launched : 2014
Journal of Family Medicine and Community Health
ISSN : 2379-0547
Launched : 2013
Annals of Pregnancy and Care
ISSN : 2578-336X
Launched : 2017
JSM Cell and Developmental Biology
ISSN : 2379-061X
Launched : 2013
Annals of Aquaculture and Research
ISSN : 2379-0881
Launched : 2014
Clinical Research in Pulmonology
ISSN : 2333-6625
Launched : 2013
Journal of Immunology and Clinical Research
ISSN : 2333-6714
Launched : 2013
Annals of Forensic Research and Analysis
ISSN : 2378-9476
Launched : 2014
JSM Biochemistry and Molecular Biology
ISSN : 2333-7109
Launched : 2013
Annals of Breast Cancer Research
ISSN : 2641-7685
Launched : 2016
Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
TEST Journal of Dentistry
ISSN : 1234-5678
Launched : 2014
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
Author Information X