As part of a year-long celebration in honor of Blood's 70th anniversary, we are publishing a series of editorials written by past Editors-in-Chief of the journal. The authors reflect on their experience at Blood in light of the journal's publication history. Each of these special pieces will highlight and discuss the impact of one or more original research articles that had a significant influence on the field or that mark a pioneering scientific development in hematology that appeared in the journal during the author's term as Editor-in-Chief.

I had the great privilege and good fortune of serving as Editor-in-Chief of Blood from 2003 to 2007, a period of important advancements in the field of hematology and of new challenges and opportunities for this and other biomedical journals. I was trained to be an editor at an early age during an era of mechanical typewriters and carbon paper, and just before the birth of this journal (Figure 1). The success of Blood from 2003 to 2007 was made possible largely through the efforts of a group of talented and collegial Associate Editors, an Editorial Board committed to participating in rigorous peer review, dedicated publication professionals in Blood’s central office in Washington, DC, and an arm’s length but supportive relationship between the American Society of Hematology and the editorial apparatus of the journal. During this 5-year period, manuscript submissions to Blood increased from ∼3000 per year to >5000 per year, with the acceptance rate remaining relatively constant at ∼25%.

Figure 1

The early training of a Blood editor, circa 1944. This untouched photograph was taken by Arthur Shattil.

Figure 1

The early training of a Blood editor, circa 1944. This untouched photograph was taken by Arthur Shattil.

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There were many important, even breakthrough, hematology research papers published in Blood between 2003 and 2007. I can recall several in particular that broadened my knowledge of the field and that have stood the test of time and influenced subsequent basic and clinical research and patient care. Examples from my top 10 list include (in no particular order of importance):

  1. Demonstration of improved outcome for children with acute lymphoblastic leukemia in the Total Therapy Study XIIIB.1 

  2. Demonstration of significant clinical and cytogenetic responses to dasatinib2  or nilotinib3  in Bcr-Abl-positive chronic myelogenous leukemia, including after the development of treatment resistance to imatinib. These drugs were also shown be effective, albeit to a lesser extent, in some cases of accelerated phase4  or blast crisis5  chronic myelogenous leukemia.

  3. Clarification of the pathobiological and clinical significance of mutations in Jak26-9  in patients with polycythemia vera, essential thrombocythemia, or myelofibrosis. Additional reports illustrated the diagnostic and clinical significance of mutations in MPL in individuals with Jak2 (V627F)–negative essential thrombocythemia,10  or in VHL in Chuvash congenital polycythemia.11,12 

  4. Identification by fluorescence in situ hybridization of deletion of the CHIC2 locus as a surrogate for the FIP1L1-PDGFRA fusion protein in systemic mastocytosis associated with eosinophilia, a predictor of response to imatinib in this disorder.13  Other individuals with systemic mastocytosis may exhibit a KIT(D816V) mutation in their bone marrow mast cells and CD34-positive hematopoietic progenitor cells,14  portending a lack of response to imatinib.

  5. Clarification of the Blackfan-Diamond15-17  and Shwachman-Diamond18  inherited bone marrow failure syndromes as disorders of ribosome expression or function.

  6. Continuation of efforts to reduce morbidity and mortality in individuals suffering from sickle cell anemia.19-22 

  7. Investigations into the role of hepcidin and other genes in normal iron metabolism and in disease states, including hereditary hemochromatosis and the anemia of chronic disease.23-34 

  8. Further demonstration of the therapeutic efficacy of eculizumab in paroxysmal nocturnal hemoglobinuria.35,36 

  9. Studies into the epidemiology and potential etiologies of transfusion-associated lung injury (TRALI),37  eventually leading to a change in transfusion practices that have reduced the incidence of this serious complication following blood transfusion.

  10. Demonstration in mice that recombinant proteins such as factor VIII and urokinase-type plasminogen activator can be expressed in megakaryocytes and platelets, providing proof of principle that platelets may serve as a potential delivery system for therapeutic proteins in disorders of hemostasis or thrombosis.38,39  This work preceded by several years the generation of induced pluripotent stem cells from human somatic cells, a feat that has accelerated current efforts aimed at producing genetically modified megakaryocytes and platelets for therapeutic purposes.

What about new opportunities for Blood during my tenure as Editor-in-Chief? A series called Translational Reviews in Hematology and another called Blood Work were introduced in the journal during this period of time. The purpose of Translational Reviews was to shine light on subject areas in which basic research was informing diagnostic and therapeutic advances in nonmalignant and malignant blood disorders. The purpose of Blood Work was to bring to each issue of the journal a photomicrograph containing an interesting, pedagogical, or unusual peripheral blood smear or bone marrow. The latter series was initiated in response to concern that hematology trainees were in danger of becoming less and less exposed to the diagnostic power of the blood smear in an era of information overload and of ill-fated attempts at multitasking.40  It is gratifying to see that this series is still going strong, and it may become increasingly important as blood smear production and analysis are taken over by robots that never took a hematology fellowship. I am no Luddite, but in my view, no digital image can match the beauty and utility of a well-made peripheral blood smear examined directly under the light microscope.

Blood faced several challenges between 2003 and 2007. First, the improper use of digital images was becoming a palpable problem in scientific publishing.41  In response, we introduced a system into the editorial process to examine all such images in accepted manuscripts to educate authors on acceptable practices and to better detect inappropriate image manipulation, be it willful or unintentional.42  Guidelines for image preparation remain an important feature of Blood’s current Author Guide.

Second, in the early years of this century, publishers of biomedical journals sponsored by learned societies such as the American Society of Hematology became increasingly concerned with the growth of the open access movement, which was perceived as threatening the business models of journals like Blood. Our stance was to welcome further efforts to open access,43  but in ways that preserved the key peer-review function of the journal and its scientific rigor and financial viability. So far, so good, although models of scientific publishing continue to be a moving target.

Third, while serving as Editor-in-Chief, I frequently railed against the widespread and, to my mind, inappropriate use of journal impact factors in assessing the quality of individual published manuscripts and their authors. This remains a major problem. As recently articulated by the San Francisco Declaration on Research Assessment (http://www.ascb.org/dora/), there need to be better ways to evaluate research by academic institutions, funding agencies, and scientists themselves than journal-based impact factors. It may take a while to turn this ship around, and metrics that better assess the quality of a piece of work, its reproducibility, and its eventual impact are needed. Although I no longer speak for Blood, top journals like it should do their part and end the tyranny of the impact factor.

The Nobel laureate George Richards Minot wrote in the foreword to the first issue of Blood in 1946: “The best clinical investigator must be an able clinician, have wide interests, and understand human beings. He must possess an active, creative imagination and scientific curiosity, but the center of his activity must be the patient. Much knowledge and progressive interest has developed concerning the blood and its disorders … so that now one may feel that a medical journal in English devoted to this subject is appropriate.”44  Minot’s prescience is no better illustrated than in the current pages of Blood. It was an honor to have played a small part in the journal’s history. Happy birthday, Blood!

I thank Drs Jim Griffin and Ken Kaushansky for asking me to serve as an Associate Editor of Blood prior to my service as Editor-in-Chief. This service could not have been performed without the dedication and expertise of my Associate Editors, the editorial and production staff of the journal, and wise input from the Publications Committee of the American Society of Hematology.

1
Pui
 
CH
Sandlund
 
JT
Pei
 
D
et al. 
Total Therapy Study XIIIB at St Jude Children’s Research Hospital
Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children’s Research Hospital.
Blood
2004
, vol. 
104
 
9
(pg. 
2690
-
2696
)
2
Hochhaus
 
A
Kantarjian
 
HM
Baccarani
 
M
et al. 
Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy.
Blood
2007
, vol. 
109
 
6
(pg. 
2303
-
2309
)
3
Kantarjian
 
HM
Giles
 
F
Gattermann
 
N
et al. 
Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance.
Blood
2007
, vol. 
110
 
10
(pg. 
3540
-
3546
)
4
le Coutre
 
P
Ottmann
 
OG
Giles
 
F
et al. 
Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is active in patients with imatinib-resistant or -intolerant accelerated-phase chronic myelogenous leukemia.
Blood
2008
, vol. 
111
 
4
(pg. 
1834
-
1839
)
5
Cortes
 
J
Rousselot
 
P
Kim
 
DW
et al. 
Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis.
Blood
2007
, vol. 
109
 
8
(pg. 
3207
-
3213
)
6
Kralovics
 
R
Teo
 
SS
Li
 
S
et al. 
Acquisition of the V617F mutation of JAK2 is a late genetic event in a subset of patients with myeloproliferative disorders.
Blood
2006
, vol. 
108
 
4
(pg. 
1377
-
1380
)
7
Lippert
 
E
Boissinot
 
M
Kralovics
 
R
et al. 
The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera.
Blood
2006
, vol. 
108
 
6
(pg. 
1865
-
1867
)
8
Scott
 
LM
Scott
 
MA
Campbell
 
PJ
Green
 
AR
Progenitors homozygous for the V617F mutation occur in most patients with polycythemia vera, but not essential thrombocythemia.
Blood
2006
, vol. 
108
 
7
(pg. 
2435
-
2437
)
9
Campbell
 
PJ
Baxter
 
EJ
Beer
 
PA
et al. 
Mutation of JAK2 in the myeloproliferative disorders: timing, clonality studies, cytogenetic associations, and role in leukemic transformation.
Blood
2006
, vol. 
108
 
10
(pg. 
3548
-
3555
)
10
Pardanani
 
AD
Levine
 
RL
Lasho
 
T
et al. 
MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients.
Blood
2006
, vol. 
108
 
10
(pg. 
3472
-
3476
)
11
Pastore
 
YD
Jelinek
 
J
Ang
 
S
et al. 
Mutations in the VHL gene in sporadic apparently congenital polycythemia.
Blood
2003
, vol. 
101
 
4
(pg. 
1591
-
1595
)
12
Liu
 
E
Percy
 
MJ
Amos
 
CI
et al. 
The worldwide distribution of the VHL 598C>T mutation indicates a single founding event.
Blood
2004
, vol. 
103
 
5
(pg. 
1937
-
1940
)
13
Pardanani
 
A
Ketterling
 
RP
Brockman
 
SR
et al. 
CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy.
Blood
2003
, vol. 
102
 
9
(pg. 
3093
-
3096
)
14
Garcia-Montero
 
AC
Jara-Acevedo
 
M
Teodosio
 
C
et al. 
KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders: a prospective study of the Spanish Network on Mastocytosis (REMA) in a series of 113 patients.
Blood
2006
, vol. 
108
 
7
(pg. 
2366
-
2372
)
15
Ebert
 
BL
Lee
 
MM
Pretz
 
JL
et al. 
An RNA interference model of RPS19 deficiency in Diamond-Blackfan anemia recapitulates defective hematopoiesis and rescue by dexamethasone: identification of dexamethasone-responsive genes by microarray.
Blood
2005
, vol. 
105
 
12
(pg. 
4620
-
4626
)
16
Flygare
 
J
Kiefer
 
T
Miyake
 
K
et al. 
Deficiency of ribosomal protein S19 in CD34+ cells generated by siRNA blocks erythroid development and mimics defects seen in Diamond-Blackfan anemia.
Blood
2005
, vol. 
105
 
12
(pg. 
4627
-
4634
)
17
Choesmel
 
V
Bacqueville
 
D
Rouquette
 
J
et al. 
Impaired ribosome biogenesis in Diamond-Blackfan anemia.
Blood
2007
, vol. 
109
 
3
(pg. 
1275
-
1283
)
18
Ganapathi
 
KA
Austin
 
KM
Lee
 
CS
et al. 
The human Shwachman-Diamond syndrome protein, SBDS, associates with ribosomal RNA.
Blood
2007
, vol. 
110
 
5
(pg. 
1458
-
1465
)
19
Ware
 
RE
Zimmerman
 
SA
Sylvestre
 
PB
et al. 
Prevention of secondary stroke and resolution of transfusional iron overload in children with sickle cell anemia using hydroxyurea and phlebotomy.
J Pediatr
2004
, vol. 
145
 
3
(pg. 
346
-
352
)
20
Lee
 
MT
Piomelli
 
S
Granger
 
S
et al. 
STOP Study Investigators
Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results.
Blood
2006
, vol. 
108
 
3
(pg. 
847
-
852
)
21
Adams
 
RJ
Brambilla
 
DJ
Granger
 
S
et al. 
STOP Study
Stroke and conversion to high risk in children screened with transcranial Doppler ultrasound during the STOP study.
Blood
2004
, vol. 
103
 
10
(pg. 
3689
-
3694
)
22
Quinn
 
CT
Rogers
 
ZR
Buchanan
 
GR
Survival of children with sickle cell disease.
Blood
2004
, vol. 
103
 
11
(pg. 
4023
-
4027
)
23
Ganz
 
T
Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation.
Blood
2003
, vol. 
102
 
3
(pg. 
783
-
788
)
24
Porto
 
G
Roetto
 
A
Daraio
 
F
et al. 
A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron.
Blood
2005
, vol. 
106
 
8
(pg. 
2922
-
2923
)
25
Nemeth
 
E
Preza
 
GC
Jung
 
CL
Kaplan
 
J
Waring
 
AJ
Ganz
 
T
The N-terminus of hepcidin is essential for its interaction with ferroportin: structure-function study.
Blood
2006
, vol. 
107
 
1
(pg. 
328
-
333
)
26
Lin
 
L
Goldberg
 
YP
Ganz
 
T
Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin.
Blood
2005
, vol. 
106
 
8
(pg. 
2884
-
2889
)
27
Rivera
 
S
Nemeth
 
E
Gabayan
 
V
Lopez
 
MA
Farshidi
 
D
Ganz
 
T
Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs.
Blood
2005
, vol. 
106
 
6
(pg. 
2196
-
2199
)
28
Détivaud
 
L
Nemeth
 
E
Boudjema
 
K
et al. 
Hepcidin levels in humans are correlated with hepatic iron stores, hemoglobin levels, and hepatic function.
Blood
2005
, vol. 
106
 
2
(pg. 
746
-
748
)
29
Rivera
 
S
Liu
 
L
Nemeth
 
E
Gabayan
 
V
Sorensen
 
OE
Ganz
 
T
Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia.
Blood
2005
, vol. 
105
 
4
(pg. 
1797
-
1802
)
30
Nemeth
 
E
Roetto
 
A
Garozzo
 
G
Ganz
 
T
Camaschella
 
C
Hepcidin is decreased in TFR2 hemochromatosis.
Blood
2005
, vol. 
105
 
4
(pg. 
1803
-
1806
)
31
Papanikolaou
 
G
Tzilianos
 
M
Christakis
 
JI
et al. 
Hepcidin in iron overload disorders.
Blood
2005
, vol. 
105
 
10
(pg. 
4103
-
4105
)
32
Mims
 
MP
Guan
 
Y
Pospisilova
 
D
et al. 
Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload.
Blood
2005
, vol. 
105
 
3
(pg. 
1337
-
1342
)
33
Lesbordes-Brion
 
JC
Viatte
 
L
Bennoun
 
M
et al. 
Targeted disruption of the hepcidin 1 gene results in severe hemochromatosis.
Blood
2006
, vol. 
108
 
4
(pg. 
1402
-
1405
)
34
Viatte
 
L
Nicolas
 
G
Lou
 
DQ
et al. 
Chronic hepcidin induction causes hyposideremia and alters the pattern of cellular iron accumulation in hemochromatotic mice.
Blood
2006
, vol. 
107
 
7
(pg. 
2952
-
2958
)
35
Hill
 
A
Hillmen
 
P
Richards
 
SJ
et al. 
Sustained response and long-term safety of eculizumab in paroxysmal nocturnal hemoglobinuria.
Blood
2005
, vol. 
106
 
7
(pg. 
2559
-
2565
)
36
Hillmen
 
P
Muus
 
P
Dührsen
 
U
et al. 
Effect of the complement inhibitor eculizumab on thromboembolism in patients with paroxysmal nocturnal hemoglobinuria.
Blood
2007
, vol. 
110
 
12
(pg. 
4123
-
4128
)
37
Silliman
 
CC
Boshkov
 
LK
Mehdizadehkashi
 
Z
et al. 
Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors.
Blood
2003
, vol. 
101
 
2
(pg. 
454
-
462
)
38
Kufrin
 
D
Eslin
 
DE
Bdeir
 
K
et al. 
Antithrombotic thrombocytes: ectopic expression of urokinase-type plasminogen activator in platelets.
Blood
2003
, vol. 
102
 
3
(pg. 
926
-
933
)
39
Yarovoi
 
HV
Kufrin
 
D
Eslin
 
DE
et al. 
Factor VIII ectopically expressed in platelets: efficacy in hemophilia A treatment.
Blood
2003
, vol. 
102
 
12
(pg. 
4006
-
4013
)
40
Shattil
 
SJ
A (blood) smear campaign.
Blood
2003
, vol. 
101
 
7
pg. 
2453
 
41
Rossner
 
M
Yamada
 
KM
What’s in a picture? The temptation of image manipulation.
J Cell Biol
2004
, vol. 
166
 
1
(pg. 
11
-
15
)
42
Shattil
 
SJ
A digital exam for hematologists.
Blood
2007
, vol. 
109
 
6
pg. 
2275
 
43
Shattil
 
SJ
Open access, yes! Open excess, no!
Blood
2004
, vol. 
103
 
9
pg. 
3257
 
44
Minot
 
GR
Foreword to Blood, The Journal of Hematology.
Blood
1946
, vol. 
1
 
1
(pg. 
1
-
2
)
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