Accepted Article
Accepted Date: 16-Apr-2014 Article Type: Letter to the Editor
Presence of paroxysmal nocturnal hemoglobinuria (PNH) clones does not exclude inherited bone marrow failure syndromes (IBMFS)
Thein Hlaing Oo, MD The University of Texas M.D. Anderson cancer Center, Houston, USA
Running title: PNH clones in bone marrow failure states (Conflicts of interest: none) (IRB approval: not applicable) (Financial support: none)
Contact information Thein Hlaing Oo, MD The University of Texas M.D. Anderson Cancer Center Section of Thrombosis & Benign Hematology, Unit 1464 1515 Holcombe Blvd Houston, TX 77030 USA Tel: 713-563-4260 Fax: 713-563-4443 Email: [email protected] Dear Editor I was reading the manuscript by DeZern et al. with interest. The authors stated that “the presence of GPI anchor-deficient cells in at least two lineages, especially in patients with no family history of bone marrow failure or other stigma of IBMFS, virtually excludes the diagnosis of IBMFS thereby eliminating the need for additional This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ejh.12351 This article is protected by copyright. All rights reserved.
Accepted Article
costly tests and delay in initiating definitive therapy”. The authors made this conclusion based on their study comprising of only 20 patients with IBMFS [1]. I believe this conclusion is premature because of the following reasons.
The IBMFS are very rare. The overall incidence of Fanconi anemia (FA), the most common of all IBMFS, is 1/360,000 live births [2]. The chance of detecting PNH clones in IBMFS is pretty low. However, there were two reported cases of clinical PNH arising from FA patients [3, 4]. The earliest description by Sir John Dacie of the association of PNH and FA dated back to 1944 [3]. The second case was a 9-year-old girl with FA who developed PNH 3.5 years after FA diagnosis [4]. The exact etiology of the relative growth advantage of PNH clones in a damaged bone marrow remains unknown. However, it has been postulated that the PNH clonal expansion is the result of phenotypically normal cells undergoing apoptosis [5,6]. PNH may be viewed as nature gene’s therapy to attempt to restore albeit abnormal hematopoiesis to the damaged bone marrow [5]. So, it is possible that PNH clones can be detected in IBMFS. It is just extremely rare. Therefore, the presence of PNH clones does not virtually exclude IBMFS. References:
[1] Dezern AE, Symons HJ, Resar LS, Borowitz MJ, Armanios MY, Brodsky RA. Detection of paroxysmal nocturnal hemoglobinuria clones to exclude inherited bone marrow failure syndromes. Eur J Haematol. 2014 Feb 25. doi: 10.1111/ejh.12299. [Epub ahead of print]
This article is protected by copyright. All rights reserved.
Accepted Article
[2] Giri N. The inherited bone marrow failure syndromes. Hematologia 2004;8:57-59
[3] Dacie JV, Gilpin A. Refractory Anaemi (Fanconi type). Arch Dis Child 1944;19:155-162
[4] Wainwright L, Brodsky RA, Erasmus LK, Poyiadjis S, Naidu G, MacKinnon D.Paroxysmal nocturnal hemoglobinuria arising from Fanconi anemia. J Pediatr Hematol Oncol. 2003; 25:167-8.
[5] Johnson RJ, Hillmen P. Paroxysmal nocturnal hemoglobinuria: Nature’s gene therapy? Mol Pathol 2002;55:145–152
[6] Young NS, Meyers G, Schrezenmeier H, Hillmen P, Hill A. The management of paroxysmal nocturnal hemoglobinuria: recent advances in diagnosis and treatment and new hope for patients. Semin Hematol. 2009 Jan;46(1 Suppl 1):S1-S16.
This article is protected by copyright. All rights reserved.
Accepted Date: 16-Apr-2014 Article Type: Letter to the Editor
Presence of paroxysmal nocturnal hemoglobinuria (PNH) clones does not exclude inherited bone marrow failure syndromes (IBMFS)
Thein Hlaing Oo, MD The University of Texas M.D. Anderson cancer Center, Houston, USA
Running title: PNH clones in bone marrow failure states (Conflicts of interest: none) (IRB approval: not applicable) (Financial support: none)
Contact information Thein Hlaing Oo, MD The University of Texas M.D. Anderson Cancer Center Section of Thrombosis & Benign Hematology, Unit 1464 1515 Holcombe Blvd Houston, TX 77030 USA Tel: 713-563-4260 Fax: 713-563-4443 Email: [email protected] Dear Editor I was reading the manuscript by DeZern et al. with interest. The authors stated that “the presence of GPI anchor-deficient cells in at least two lineages, especially in patients with no family history of bone marrow failure or other stigma of IBMFS, virtually excludes the diagnosis of IBMFS thereby eliminating the need for additional This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/ejh.12351 This article is protected by copyright. All rights reserved.
Accepted Article
costly tests and delay in initiating definitive therapy”. The authors made this conclusion based on their study comprising of only 20 patients with IBMFS [1]. I believe this conclusion is premature because of the following reasons.
The IBMFS are very rare. The overall incidence of Fanconi anemia (FA), the most common of all IBMFS, is 1/360,000 live births [2]. The chance of detecting PNH clones in IBMFS is pretty low. However, there were two reported cases of clinical PNH arising from FA patients [3, 4]. The earliest description by Sir John Dacie of the association of PNH and FA dated back to 1944 [3]. The second case was a 9-year-old girl with FA who developed PNH 3.5 years after FA diagnosis [4]. The exact etiology of the relative growth advantage of PNH clones in a damaged bone marrow remains unknown. However, it has been postulated that the PNH clonal expansion is the result of phenotypically normal cells undergoing apoptosis [5,6]. PNH may be viewed as nature gene’s therapy to attempt to restore albeit abnormal hematopoiesis to the damaged bone marrow [5]. So, it is possible that PNH clones can be detected in IBMFS. It is just extremely rare. Therefore, the presence of PNH clones does not virtually exclude IBMFS. References:
[1] Dezern AE, Symons HJ, Resar LS, Borowitz MJ, Armanios MY, Brodsky RA. Detection of paroxysmal nocturnal hemoglobinuria clones to exclude inherited bone marrow failure syndromes. Eur J Haematol. 2014 Feb 25. doi: 10.1111/ejh.12299. [Epub ahead of print]
This article is protected by copyright. All rights reserved.
Accepted Article
[2] Giri N. The inherited bone marrow failure syndromes. Hematologia 2004;8:57-59
[3] Dacie JV, Gilpin A. Refractory Anaemi (Fanconi type). Arch Dis Child 1944;19:155-162
[4] Wainwright L, Brodsky RA, Erasmus LK, Poyiadjis S, Naidu G, MacKinnon D.Paroxysmal nocturnal hemoglobinuria arising from Fanconi anemia. J Pediatr Hematol Oncol. 2003; 25:167-8.
[5] Johnson RJ, Hillmen P. Paroxysmal nocturnal hemoglobinuria: Nature’s gene therapy? Mol Pathol 2002;55:145–152
[6] Young NS, Meyers G, Schrezenmeier H, Hillmen P, Hill A. The management of paroxysmal nocturnal hemoglobinuria: recent advances in diagnosis and treatment and new hope for patients. Semin Hematol. 2009 Jan;46(1 Suppl 1):S1-S16.
This article is protected by copyright. All rights reserved.
