DOI: 10.1046/j.1365-2141.2002.03599.x. Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124 patients

Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124 patients

10.1046/j.1365-2141.2002.03599.x

Crossref journal-article

Wiley

British Journal of Haematology (311)

Abstract

Summary. The French–American–British (FAB) classification and the new World Health Organization (WHO) classification distinguish acute monoblastic leukaemia (AML M5a) from acute monocytic leukaemia (AML M5b). Not much is known about the underlying genetic differences leading to these clearly different phenotypes. We analysed 58 patients with de novo AML M5a and 66 patients with denovo AML M5b in comparison with a whole group of 1603 de novo AML. An aberrant karyotype was found in 75·9% of AML M5a but in only 28·8% of M5b (P < 0·0001) and in 54·7% of all other AML subtypes (P = 0·0015). 11q23/MLL aberrations were detected in 31% of M5a, 12·1% of M5b (P = 0·01) but only 1·3% of all other AML subtypes (P < 0·0001). Trisomy 8 as the sole cytogenetic aberration was found in 22·4% of M5a, but in only 3% of M5b and in 2·5% of all other AML subcategories (P < 0·0001). Although the frequency of the MLL‐partial tandem duplication (MLL‐PTD) did not differ between the three cohorts (1·7%, 4·5% and 6·1% respectively, NS), thedetection of FLT3 length mutations (FLT3‐LM) differed significantly. AML M5a showed a low frequency of only 6·9%, but 28·8% of M5b (P = 0·0014) and 23·5% of all other AML revealed a FLT3‐LM. In conclusion, we demonstrated genetic, i.e. biological, differences between AML M5a and AML M5b and all other AML. Therefore, AML M5 should further be categorized as two different groups, as proposed by the WHO classification.

Bibliography

Haferlach, T., Schoch, C., Schnittger, S., Kern, W., LÃ¶ffler, H., & Hiddemann, W. (2002). Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124 patients. British Journal of Haematology, 118(2), 426â431. Portico.

Authors 6

Torsten Haferlach (first)
Claudia Schoch (additional)
Susanne Schnittger (additional)
Wolfgang Kern (additional)
Helmut Löffler (additional)
Wolfgang Hiddemann (additional)

References 32 Referenced 45

10.1111/j.1365-2141.1976.tb03563.x
10.1111/j.1365-2141.1980.tb01195.x
10.7326/0003-4819-103-4-620
10.7326/0003-4819-103-3-460
10.1111/j.1365-2141.1991.tb04444.x
10.1016/0145-2126(82)90039-X
{'key': 'e_1_2_5_8_1', 'first-page': '75', 'volume-title': 'World Health Organization of Tumors. Pathology and Genetics. Tumors of Haematopoietic and Lymphoid Tissues', 'author': 'Brunning R.D.', 'year': '2001'} / World Health Organization of Tumors. Pathology and Genetics. Tumors of Haematopoietic and Lymphoid Tissues by Brunning R.D. (2001)
{'key': 'e_1_2_5_9_1', 'first-page': '4116', 'article-title': 'Double induction strategy for acute myeloid leukemia: the effect of high‐dose cytarabine with mitoxantrone instead of standard‐dose cytarabine with daunorubicin and 6‐thioguanine: a randomized trial by the German AML Cooperative Group', 'volume': '93', 'author': 'Büchner T.', 'year': '1999', 'journal-title': 'Blood'} / Blood / Double induction strategy for acute myeloid leukemia: the effect of high‐dose cytarabine with mitoxantrone instead of standard‐dose cytarabine with daunorubicin and 6‐thioguanine: a randomized trial by the German AML Cooperative Group by Büchner T. (1999)
10.1016/S0140-6736(97)09214-3
10.1182/blood.V64.1.237.237 / Blood / TdT‐positive acute leukemia with monocytoid characteristcs: clinical, cytochemical, cytogenetic, and immunologic findings by Cuttner J. (1984)
{'key': 'e_1_2_5_12_1', 'first-page': '291a', 'article-title': 'Cytomorphology and cytogenetics in de novo AML: importance for the definition of biological entities', 'volume': '94', 'author': 'Haferlach T.', 'year': '1999', 'journal-title': 'Blood'} / Blood / Cytomorphology and cytogenetics in de novo AML: importance for the definition of biological entities by Haferlach T. (1999)
10.1182/blood.V89.7.2311 / Blood / Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML 10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council by Hann I.M. (1997)
{'key': 'e_1_2_5_14_1', 'first-page': '2978', 'article-title': 'Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucemies Aigues Myeloblastique (GOELAM)', 'volume': '90', 'author': 'Harousseau J.L.', 'year': '1997', 'journal-title': 'Blood'} / Blood / Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucemies Aigues Myeloblastique (GOELAM) by Harousseau J.L. (1997)
10.1200/JCO.1999.17.12.3835
{'key': 'e_1_2_5_16_1', 'volume-title': 'Guidelines for Cancer Cytogenetics, Supplement to: An International System for Human Cytogenetic Nomenclature', 'author': 'ISCN', 'year': '1995'} / Guidelines for Cancer Cytogenetics, Supplement to: An International System for Human Cytogenetic Nomenclature by ISCN (1995)
{'key': 'e_1_2_5_17_1', 'volume-title': 'Atlas of Clinical Hematology.', 'author': 'Löffler H.', 'year': '1999'} / Atlas of Clinical Hematology. by Löffler H. (1999)
10.1056/NEJM199410063311402
10.1093/nar/16.3.1215
{'key': 'e_1_2_5_20_1', 'first-page': '210', 'article-title': 'Detection of four different 11q23 chromosomal abnormalities by multiplex‐PCR and fluorescence‐based automatic DNA‐fragment analysis', 'volume': '9', 'author': 'Repp R.', 'year': '1995', 'journal-title': 'Leukemia'} / Leukemia / Detection of four different 11q23 chromosomal abnormalities by multiplex‐PCR and fluorescence‐based automatic DNA‐fragment analysis by Repp R. (1995)
10.1111/j.1365-2141.1986.tb02211.x
{'key': 'e_1_2_5_22_1', 'first-page': '4277', 'article-title': 'ALL‐1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements', 'volume': '54', 'author': 'Schichman S.A.', 'year': '1994', 'journal-title': 'Cancer Research'} / Cancer Research / ALL‐1 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements by Schichman S.A. (1994)
10.1182/blood.V92.5.1728
10.1038/sj.leu.2401773
{'key': 'e_1_2_5_25_1', 'first-page': '801a', 'article-title': 'Partial tandem duplication (PTD) of the MLL gene: a study of 1603 patients reveals high frequency in secondary acute myeloid leukemia and low association with trisomy 11', 'volume': '98', 'author': 'Schnittger S.', 'year': '2001', 'journal-title': 'Blood'} / Blood / Partial tandem duplication (PTD) of the MLL gene: a study of 1603 patients reveals high frequency in secondary acute myeloid leukemia and low association with trisomy 11 by Schnittger S. (2001)
{'key': 'e_1_2_5_26_1', 'first-page': '581a', 'article-title': 'FLT3‐LM and MLL‐PTD as markers for PCR‐based detection of minimal residual disease (MRD) in AML with normal karyotype', 'volume': '98', 'author': 'Schnittger S.', 'year': '2001', 'journal-title': 'Blood'} / Blood / FLT3‐LM and MLL‐PTD as markers for PCR‐based detection of minimal residual disease (MRD) in AML with normal karyotype by Schnittger S. (2001)
{'key': 'e_1_2_5_27_1', 'first-page': '92a', 'article-title': 'Specific abnormalities on the genomic level result in a distinct gene expression pattern detected by oligonucleotide microarrays: An analysis of 25 patients with AML M2/t(8;21), AML M3/M3v/t(15;17), and AML M4eo/inv(16)', 'volume': '98', 'author': 'Schoch C.', 'year': '2001', 'journal-title': 'Blood'} / Blood / Specific abnormalities on the genomic level result in a distinct gene expression pattern detected by oligonucleotide microarrays: An analysis of 25 patients with AML M2/t(8;21), AML M3/M3v/t(15;17), and AML M4eo/inv(16) by Schoch C. (2001)
10.1038/sj.leu.2402329
10.1016/0165-4608(88)90087-8
10.1182/blood.V55.1.71.71
10.1073/pnas.98.3.1124
10.1182/blood.V88.8.2841.bloodjournal8882841 / Blood / A randomized investigation of high‐dose versus standard‐dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a South West Oncology Group Study by Weick J.K. (1996)
10.1056/NEJM199501263320403

Dates

Type	When
Created	22 years, 5 months ago (March 11, 2003, 1:46 a.m.)
Deposited	1 year, 10 months ago (Oct. 15, 2023, 10:07 p.m.)
Indexed	1 year, 2 months ago (June 10, 2024, 3:54 p.m.)
Issued	23 years, 1 month ago (July 25, 2002)
Published	23 years, 1 month ago (July 25, 2002)
Published Online	23 years, 1 month ago (July 25, 2002)
Published Print	23 years, 1 month ago (Aug. 1, 2002)

Funders 0

None

BibTeX

@article{Haferlach_2002, title={Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124 patients}, volume={118}, ISSN={1365-2141}, url={http://dx.doi.org/10.1046/j.1365-2141.2002.03599.x}, DOI={10.1046/j.1365-2141.2002.03599.x}, number={2}, journal={British Journal of Haematology}, publisher={Wiley}, author={Haferlach, Torsten and Schoch, Claudia and Schnittger, Susanne and Kern, Wolfgang and Löffler, Helmut and Hiddemann, Wolfgang}, year={2002}, month=jul, pages={426–431} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2024,
        6,
        10
      ]
    ],
    "date-time": "2024-06-10T19:54:49Z",
    "timestamp": 1718049289401
  },
  "reference-count": 32,
  "publisher": "Wiley",
  "issue": "2",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2002,
            7,
            25
          ]
        ],
        "date-time": "2002-07-25T00:00:00Z",
        "timestamp": 1027555200000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [
      "onlinelibrary.wiley.com"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        2002,
        8
      ]
    ]
  },
  "abstract": "<jats:p><jats:bold>Summary.</jats:bold> The French\u2013American\u2013British (FAB) classification and the new World Health Organization (WHO) classification distinguish acute monoblastic leukaemia (AML M5a) from acute monocytic leukaemia (AML M5b). Not much is known about the underlying genetic differences leading to these clearly different phenotypes. We analysed 58 patients with <jats:italic>de novo</jats:italic> AML M5a and 66 patients with <jats:italic>denovo</jats:italic> AML M5b in comparison with a whole group of 1603 <jats:italic>de novo</jats:italic> AML. An aberrant karyotype was found in 75\u00b79% of AML M5a but in only 28\u00b78% of M5b (<jats:italic>P</jats:italic>\u2003&lt;\u20030\u00b70001) and in 54\u00b77% of all other AML subtypes (<jats:italic>P</jats:italic>\u2003=\u20030\u00b70015). 11q23/MLL aberrations were detected in 31% of M5a, 12\u00b71% of M5b (<jats:italic>P</jats:italic>\u2003=\u20030\u00b701) but only 1\u00b73% of all other AML subtypes (<jats:italic>P</jats:italic>\u2003&lt;\u20030\u00b70001). Trisomy 8 as the sole cytogenetic aberration was found in 22\u00b74% of M5a, but in only 3% of M5b and in 2\u00b75% of all other AML subcategories (<jats:italic>P</jats:italic>\u2003&lt;\u20030\u00b70001). Although the frequency of the MLL\u2010partial tandem duplication (MLL\u2010PTD) did not differ between the three cohorts (1\u00b77%, 4\u00b75% and 6\u00b71% respectively, NS), thedetection of FLT3 length mutations (FLT3\u2010LM) differed significantly. AML M5a showed a low frequency of only 6\u00b79%, but 28\u00b78% of M5b (<jats:italic>P</jats:italic>\u2003=\u20030\u00b70014) and 23\u00b75% of all other AML revealed a FLT3\u2010LM. In conclusion, we demonstrated genetic, i.e. biological, differences between AML M5a and AML M5b and all other AML. Therefore, AML M5 should further be categorized as two different groups, as proposed by the WHO classification.</jats:p>",
  "DOI": "10.1046/j.1365-2141.2002.03599.x",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2003,
        3,
        11
      ]
    ],
    "date-time": "2003-03-11T06:46:33Z",
    "timestamp": 1047365193000
  },
  "page": "426-431",
  "update-policy": "http://dx.doi.org/10.1002/crossmark_policy",
  "source": "Crossref",
  "is-referenced-by-count": 45,
  "title": "Distinct genetic patterns can be identified in acute monoblastic and acute monocytic leukaemia (FAB AML M5a and M5b): a study of 124 patients",
  "prefix": "10.1111",
  "volume": "118",
  "author": [
    {
      "given": "Torsten",
      "family": "Haferlach",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Claudia",
      "family": "Schoch",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Susanne",
      "family": "Schnittger",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Wolfgang",
      "family": "Kern",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Helmut",
      "family": "L\u00f6ffler",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Wolfgang",
      "family": "Hiddemann",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2002,
        7,
        25
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_5_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1365-2141.1976.tb03563.x"
    },
    {
      "key": "e_1_2_5_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1365-2141.1980.tb01195.x"
    },
    {
      "key": "e_1_2_5_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.7326/0003-4819-103-4-620"
    },
    {
      "key": "e_1_2_5_5_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.7326/0003-4819-103-3-460"
    },
    {
      "key": "e_1_2_5_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1365-2141.1991.tb04444.x"
    },
    {
      "key": "e_1_2_5_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0145-2126(82)90039-X"
    },
    {
      "key": "e_1_2_5_8_1",
      "first-page": "75",
      "volume-title": "World Health Organization of Tumors. Pathology and Genetics. Tumors of Haematopoietic and Lymphoid Tissues",
      "author": "Brunning R.D.",
      "year": "2001"
    },
    {
      "key": "e_1_2_5_9_1",
      "first-page": "4116",
      "article-title": "Double induction strategy for acute myeloid leukemia: the effect of high\u2010dose cytarabine with mitoxantrone instead of standard\u2010dose cytarabine with daunorubicin and 6\u2010thioguanine: a randomized trial by the German AML Cooperative Group",
      "volume": "93",
      "author": "B\u00fcchner T.",
      "year": "1999",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0140-6736(97)09214-3"
    },
    {
      "key": "e_1_2_5_11_1",
      "doi-asserted-by": "crossref",
      "first-page": "237",
      "DOI": "10.1182/blood.V64.1.237.237",
      "article-title": "TdT\u2010positive acute leukemia with monocytoid characteristcs: clinical, cytochemical, cytogenetic, and immunologic findings",
      "volume": "64",
      "author": "Cuttner J.",
      "year": "1984",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_12_1",
      "first-page": "291a",
      "article-title": "Cytomorphology and cytogenetics in de novo AML: importance for the definition of biological entities",
      "volume": "94",
      "author": "Haferlach T.",
      "year": "1999",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_13_1",
      "doi-asserted-by": "crossref",
      "first-page": "2311",
      "DOI": "10.1182/blood.V89.7.2311",
      "article-title": "Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML 10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council",
      "volume": "89",
      "author": "Hann I.M.",
      "year": "1997",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_14_1",
      "first-page": "2978",
      "article-title": "Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucemies Aigues Myeloblastique (GOELAM)",
      "volume": "90",
      "author": "Harousseau J.L.",
      "year": "1997",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1200/JCO.1999.17.12.3835"
    },
    {
      "key": "e_1_2_5_16_1",
      "volume-title": "Guidelines for Cancer Cytogenetics, Supplement to: An International System for Human Cytogenetic Nomenclature",
      "author": "ISCN",
      "year": "1995"
    },
    {
      "key": "e_1_2_5_17_1",
      "volume-title": "Atlas of Clinical Hematology.",
      "author": "L\u00f6ffler H.",
      "year": "1999"
    },
    {
      "key": "e_1_2_5_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJM199410063311402"
    },
    {
      "key": "e_1_2_5_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1093/nar/16.3.1215"
    },
    {
      "key": "e_1_2_5_20_1",
      "first-page": "210",
      "article-title": "Detection of four different 11q23 chromosomal abnormalities by multiplex\u2010PCR and fluorescence\u2010based automatic DNA\u2010fragment analysis",
      "volume": "9",
      "author": "Repp R.",
      "year": "1995",
      "journal-title": "Leukemia"
    },
    {
      "key": "e_1_2_5_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1365-2141.1986.tb02211.x"
    },
    {
      "key": "e_1_2_5_22_1",
      "first-page": "4277",
      "article-title": "ALL\u20101 tandem duplication in acute myeloid leukemia with a normal karyotype involves homologous recombination between Alu elements",
      "volume": "54",
      "author": "Schichman S.A.",
      "year": "1994",
      "journal-title": "Cancer Research"
    },
    {
      "key": "e_1_2_5_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V92.5.1728"
    },
    {
      "key": "e_1_2_5_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.leu.2401773"
    },
    {
      "key": "e_1_2_5_25_1",
      "first-page": "801a",
      "article-title": "Partial tandem duplication (PTD) of the MLL gene: a study of 1603 patients reveals high frequency in secondary acute myeloid leukemia and low association with trisomy 11",
      "volume": "98",
      "author": "Schnittger S.",
      "year": "2001",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_26_1",
      "first-page": "581a",
      "article-title": "FLT3\u2010LM and MLL\u2010PTD as markers for PCR\u2010based detection of minimal residual disease (MRD) in AML with normal karyotype",
      "volume": "98",
      "author": "Schnittger S.",
      "year": "2001",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_27_1",
      "first-page": "92a",
      "article-title": "Specific abnormalities on the genomic level result in a distinct gene expression pattern detected by oligonucleotide microarrays: An analysis of 25 patients with AML M2/t(8;21), AML M3/M3v/t(15;17), and AML M4eo/inv(16)",
      "volume": "98",
      "author": "Schoch C.",
      "year": "2001",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_28_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/sj.leu.2402329"
    },
    {
      "key": "e_1_2_5_29_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0165-4608(88)90087-8"
    },
    {
      "key": "e_1_2_5_30_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1182/blood.V55.1.71.71"
    },
    {
      "key": "e_1_2_5_31_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.98.3.1124"
    },
    {
      "key": "e_1_2_5_32_1",
      "doi-asserted-by": "crossref",
      "first-page": "2841",
      "DOI": "10.1182/blood.V88.8.2841.bloodjournal8882841",
      "article-title": "A randomized investigation of high\u2010dose versus standard\u2010dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a South West Oncology Group Study",
      "volume": "88",
      "author": "Weick J.K.",
      "year": "1996",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_2_5_33_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJM199501263320403"
    }
  ],
  "container-title": "British Journal of Haematology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2141.2002.03599.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1365-2141.2002.03599.x",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2141.2002.03599.x",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        10,
        16
      ]
    ],
    "date-time": "2023-10-16T02:07:28Z",
    "timestamp": 1697422048000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1046/j.1365-2141.2002.03599.x"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2002,
        7,
        25
      ]
    ]
  },
  "references-count": 32,
  "journal-issue": {
    "issue": "2",
    "published-print": {
      "date-parts": [
        [
          2002,
          8
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1046/j.1365-2141.2002.03599.x"
  ],
  "URL": "http://dx.doi.org/10.1046/j.1365-2141.2002.03599.x",
  "relation": {},
  "ISSN": [
    "0007-1048",
    "1365-2141"
  ],
  "subject": [],
  "container-title-short": "Br J Haematol",
  "published": {
    "date-parts": [
      [
        2002,
        7,
        25
      ]
    ]
  },
  "assertion": [
    {
      "value": "2002-07-25",
      "order": 2,
      "name": "published",
      "label": "Published",
      "group": {
        "name": "publication_history",
        "label": "Publication History"
      }
    }
  ]
}