Infant leukaemias

Congenital leukaemias

Neonatal leukaemias

Identity

Note

infant or congenital leukaemias are defined by a diagnosis within either the first month, the first year, or the first two years of life, according to different workers; recent data have shown that patients, diagnosed to have a leukaemia at age 5 mths and 2 yrs, already had a MLL-AF4 fusion gene in their neonatal blood spots/Guthrie cards infant leukaemias have been suspected to have an environmental component: 1- some of the leukaemias known to be often related to genotoxic exposure, such as the 11q23 leukaemias and the t(8;16) leukaemia, may also be found in infants; 2- there has been a significant increase in infant acute leukaemias incidence of around 2.5% per year for 15 yrs, suggesting the presence of an environmental factor; 3- infants with leukaemia (excluding Down syndrome cases) have more congenital anomalies (heart defects, digestive tract anomalies, mental delay) they may be myelodysplasia or acute non lymphocytic leukaemia (M4 or M5 mainly) in 1/2 to 2/3 of cases, or B-cell acute lymphocytic leukaemia (CD19+ or CD10+) in the remaining cases sex ratio is balanced, both in ANLL and in ALL cases frequent CNS involvement; WBC is often high, whatever the chromosome anomaly is; skin infiltrations (leukaemia cutis) may occur 11q23 is found involved in 1/3 to 1/2 of cases (t(4;11), t(9;11), and t(11;19) representing nearly 1/10 of cases each) See also 11q23 rearrangements in childhood acute lymphoblastic leukemia: Clinical aspects 4yr event free survival in infants ALL is 1/3 and median event free survival (EFS) is 1yr in infants aged less than a month, 6 months survival is only 1/3, both in ANLL and in ALL as the prognosis is most often very poor, bone marrow transplantation is indicated, apart in infant leukemia of the Down syndrome patient, were the prognosis is good

Clinics and Pathology

Disease	Infant myelodysplasia
Note	they most often exhibit a normal karyotype or a monosomy 7
Etiology	exhibit a genetic background or is considered as idiopathic
Epidemiology	annual incidence : about 1 case per 106
Prognosis	has herein been calculated from 3 large studies (n= 47) : median survival was 31 mths; 6 yr survival was 43%

Disease	Down syndrome with M7
Note	Down syndrome patients have been known for long to be at increased risk (10 to 30 fold) of both ALL and ANLL; ALL is similar in Down syndrome (DS) and in the general population, whereas ANLL in DS is most often a specific entity of acute megakaryoblastic leukaemia (M7-ANLL); at least 20% of leukaemias in DS are M7, and other cases of M7-ANLL may also be misclassified as undifferentiated leukaemias or as ALL; therefore, the risk of M7 may well be 500 to 1000 times greater when the child has a DS; in other words, it may be that half of infants with M7 are DS ... and also that the risk of ALL in DS may not be as increased as previously claimed
Epidemiology	M7 leukaemia in Down syndrome infants annual incidence : 0.2 case per 106; median age at diagnosis is 22-23 mths
Clinics	there is often a preceeding myelodysplasia, or history of transient leukemoid reaction (a disease of the megakaryocytic lineage)
Prognosis	M7-ANLL has proved to be of better prognosis when in DS, with a recent study on 65 DS patients with M7, showing a 4 yr event free survival of 73%

Disease	11q23 abnormalities
Phenotype / cell stem origin	M4 or M5 acute non lymphocytic leukaemia (ANLL) or CD19+ B-cell acute lymphocytic leukaemia (ALL);
Epidemiology	25% of 11q23 rearrangements cases are infant (<1 yr) cases; as much as 2/3 of cases of infant ALL leukaemias have been found in some studies to carry a 11q23 rearrangement, especially in infants < 6 mths old; a third to a half of infant ANLL cases also have a 11q23 rearrangement; however, 11q23 leukaemias can also be seen in children and in adults
Clinics	organomegaly; frequent CNS involvement; high WBC
Prognosis	median survival of 1yr, and a 3yr event free survival of 13% in a study and a 4 yr event free survival of 15% in another t(4;11)(q21;q23) : CD19+ B-ALL; unbalanced sex ratio < 4 yrs (1M/2F); infants (<1 yr) accounting for 1/3 of t(4;11) cases; annual incidence could be 0.3-0.5 case per 106; prognosis: med EFS 7 mths; med survival 29mths; 3yr survival 40%; 3yr EFS: 30%; the gene involved in 4q21 is AF4 t(9;11)(p23;q23) : found in M5a or M4 ANLL; the rare ALL cases of t(9;11) are most often found in infants; infants cases (<1 yr) account for 15% of all t(9;11) cases; med EFS: 1yr, 3yr EFS 20%; the gene involved in 9p22 is AF9 t(10;11)(p12;q23) : rare; M4 or M5 ANLL; ALL at times; infants represent 40% of cases; the gene involved in 10p12 is AF10 t(11;19)(q23;p13.3): ALL, biphenotypic AL and M4 or M5 ANLL; half cases of t(11;19)(q23;p13.3) are infant cases; a study on 40 cases showed that med survival was 5 mths, with a 2yr survival of 20% (unpublished observation); the gene involved in 19p13.3 is ENL other 11q23 rearrangements are rarely found in infants leukaemias in 11q23 sits MLL, which encodes a 431 kDa protein; contains two DNA binding motifs (a AT hook, and Zinc fingers), a DNA methyl transferase motif, a bromodomain; transcriptional regulatory factor; nuclear localisation; wide expression; homology with trithorax (drosophila); the fusion protein includes the N-term AT hook and DNA methyltransferase from MLL fused to (little or most of) the partner C-term part from the other chromosome

Disease	t(1;22)(p13;q13)
Phenotype / cell stem origin	M7 ANLL
Epidemiology	39 cases so far described; <0.1 case per 106 (perhaps much less); the only leukaemia (nearly) restricted to infant cases; median age is 4 mths
Clinics	organomegaly, bone marrow fibrosis; misdiagnosis of a solid tumour is frequent
Prognosis	remission is obtained in only half cases, median survival is 7 mths

Disease	12p abnormalities
Phenotype / cell stem origin	B lineage ALL mainly (CD10+); M5 ANLL at times
Epidemiology	at least 9 cases
Prognosis	no sufficient data

Disease	inv(16)(p13q22)
Phenotype / cell stem origin	M4 ANLL
Epidemiology	at least 3 cases reported
Clinics	high WBC, CNS involvement
Prognosis	is very poor so far (remission duration : 0, 2, 6 mths), in contrast with the usual inv(16) prognosis

Disease	t(5;15)(p15;q11)
Phenotype / cell stem origin	B lineage ALL
Epidemiology	5 known cases
Prognosis	unknown; CR in 5/5

Disease	t(8;16)(p11;p13)
Phenotype / cell stem origin	M5/M4 ANLL
Epidemiology	at least 3 cases
Prognosis	survival : 0.5 mth, 22 mths+, 24 mths+

Disease	+19 and/or +21
Phenotype / cell stem origin	ANLL and ALL
Epidemiology	at least 5 cases
Prognosis	no survival data available

Disease

other chromosome rearrangements : +8 (solely or not), found in a few cases, del(6q), , and non recurring anomalies, found in at least one case each; finally, the kayotype has been found to be normal in a percentage of cases PHENOTYPE_STEM_CELL_ORIGIN

Bibliography

An analysis of leukemic cell chromosomal features in infants.

Pui CH, Raimondi SC, Murphy SB, Ribeiro RC, Kalwinsky DK, Dahl GV, Crist WM, Williams DL

Blood. 1987 ; 69 (5) : 1289-1293.

PMID 2952182

Clinical characteristics of infant acute leukemia with or without 11q23 translocations.

Kaneko Y, Shikano T, Maseki N, Sakurai M, Sakurai M, Takeda T, Hiyoshi Y, Mimaya J, Fujimoto T

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1988 ; 2 (10) : 672-676.

PMID 3172843

Phenotypic and genotypic heterogeneity in infant acute leukemia. II. Acute nonlymphoblastic leukemia.

Kˆ�ller U, Haas OA, Ludwig WD, Bartram CR, Harbott J, Panzer-Grˆºmayer R, Hansen-Hagge T, Ritter J, Creutzig U, Knapp W

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1989 ; 3 (10) : 708-714.

PMID 2779287

Acute myeloid leukemia (AML) in Down's syndrome is highly responsive to chemotherapy: experience on Pediatric Oncology Group AML Study 8498.

Ravindranath Y, Abella E, Krischer JP, Wiley J, Inoue S, Harris M, Chauvenet A, Alvarado CS, Dubowy R, Ritchey AK

Blood. 1992 ; 80 (9) : 2210-2214.

PMID 1384797

Cytogenetic features of neonatal leukemias.

Sansone R, Negri D

Cancer genetics and cytogenetics. 1992 ; 63 (1) : 56-61.

PMID 1423228

Molecular rearrangements on chromosome 11q23 predominate in infant acute lymphoblastic leukemia and are associated with specific biologic variables and poor outcome.

Chen CS, Sorensen PH, Domer PH, Reaman GH, Korsmeyer SJ, Heerema NA, Hammond GD, Kersey JH

Blood. 1993 ; 81 (9) : 2386-2393.

PMID 8481519

Cytogenetic heterogeneity in t(11;19) acute leukemia: clinical, hematological and cytogenetic analyses of 48 patients--updated published cases and 16 new observations.

Huret JL, Brizard A, Slater R, Charrin C, Bertheas MF, Guilhot F, Hˆ§hlen K, Kroes W, van Leeuwen E, Schoot EV

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1993 ; 7 (2) : 152-160.

PMID 8426468

Review of the cytogenetic changes in acute megakaryoblastic leukemia: one disease or several?

Lu G, Altman AJ, Benn PA

Cancer genetics and cytogenetics. 1993 ; 67 (2) : 81-89.

PMID 8330276

Cytogenetic features of infants less than 12 months of age at diagnosis of acute lymphoblastic leukemia: impact of the 11q23 breakpoint on outcome: a report of the Childrens Cancer Group.

Heerema NA, Arthur DC, Sather H, Albo V, Feusner J, Lange BJ, Steinherz PG, Zeltzer P, Hammond D, Reaman GH

Blood. 1994 ; 83 (8) : 2274-2284.

PMID 8161794

11q23/MLL rearrangement confers a poor prognosis in infants with acute lymphoblastic leukemia.

Pui CH, Behm FG, Downing JR, Hancock ML, Shurtleff SA, Ribeiro RC, Head DR, Mahmoud HH, Sandlund JT, Furman WL

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 1994 ; 12 (5) : 909-915.

PMID 8164041

Myelodysplasia and acute megakaryoblastic leukemia in Down's syndrome.

Zipursky A, Thorner P, De Harven E, Christensen H, Doyle J

Leukemia research. 1994 ; 18 (3) : 163-171.

PMID 8139285

[Acute myeloid leukemia in children with Down syndrome]

Creutzig U, Ritter J, Ludwig WD, Niemeyer C, Reinisch I, Stollmann-Gibbels B, Zimmermann M, Harbott J

Klinische Padiatrie. 1995 ; 207 (4) : 136-144.

PMID 7564143

Acute megakaryoblastic leukemia.

Gassman W, L?¬�ffler H

Leukemia Lymphoma. 1995 ; 18 (numero Suppl 1) : 61-63.

Pediatric myelodysplasia: a study of 68 children and a new prognostic scoring system.

Passmore SJ, Hann IM, Stiller CA, Ramani P, Swansbury GJ, Gibbons B, Reeves BR, Chessells JM

Blood. 1995 ; 85 (7) : 1742-1750.

PMID 7703482

Ultrastructural studies of the megakaryoblastic leukemias of Down syndrome.

Zipursky A, Christensen H, De Harven E

Leukemia & lymphoma. 1995 ; 18 (3-4) : 341-347.

PMID 8535203

Infant leukaemia biology, aetiology and treatment.

Greaves MF

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1996 ; 10 (2) : 372-377.

PMID 8637251

Pathogenesis, biology, and management of myelodysplastic syndromes in children.

Haas OA, Gadner H

Seminars in hematology. 1996 ; 33 (3) : 225-235.

PMID 8819232

Myelodysplastic syndrome in children: differentiation from acute myeloid leukemia with a low blast count.

Chan GC, Wang WC, Raimondi SC, Behm FG, Krance RA, Chen G, Freiberg A, Ingram L, Butler D, Head DR

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 ; 11 (2) : 206-211.

PMID 9009082

Spontaneous remission of congenital leukemia.

Dinulos JG, Hawkins DS, Clark BS, Francis JS

The Journal of pediatrics. 1997 ; 131 (2) : 300-303.

PMID 9290620

Backtracking leukemia to birth: identification of clonotypic gene fusion sequences in neonatal blood spots.

Gale KB, Ford AM, Repp R, Borkhardt A, Keller C, Eden OB, Greaves MF

Proceedings of the National Academy of Sciences of the United States of America. 1997 ; 94 (25) : 13950-13954.

PMID 9391133

Forty-four cases of childhood myelodysplasia with cytogenetics, documented by the Groupe Franˆßais de Cytogˆ©nˆ©tique Hˆ©matologique.

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 ; 11 (9) : 1478-1485.

PMID 9305601

Hematologic malignancies with t(4;11)(q21;q23)--a cytogenetic, morphologic, immunophenotypic and clinical study of 183 cases. European 11q23 Workshop participants.

Johansson B, Moorman AV, Haas OA, Watmore AE, Cheung KL, Swanton S, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 779-787.

PMID 9593281

The t(10;11)(p12;q23) translocation in acute leukaemia: a cytogenetic and clinical study of 20 patients. European 11q23 Workshop participants.

Lillington DM, Young BD, Berger R, Martineau M, Moorman AV, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 801-804.

PMID 9593284

Hematological malignancies with t(9;11)(p21-22;q23)--a laboratory and clinical study of 125 cases. European 11q23 Workshop participants.

Swansbury GJ, Slater R, Bain BJ, Moorman AV, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 792-800.

PMID 9593283

Distinctive demography, biology, and outcome of acute myeloid leukemia and myelodysplastic syndrome in children with Down syndrome: Children's Cancer Group Studies 2861 and 2891.

Lange BJ, Kobrinsky N, Barnard DR, Arthur DC, Buckley JD, Howells WB, Gold S, Sanders J, Neudorf S, Smith FO, Woods WG

Blood. 1998 ; 91 (2) : 608-615.

PMID 9427716

Congenital abnormalities in children with acute leukemia: a report from the Children's Cancer Group.

Mertens AC, Wen W, Davies SM, Steinbuch M, Buckley JD, Potter JD, Robison LL

The Journal of pediatrics. 1998 ; 133 (5) : 617-623.

PMID 9821417

The translocations, t(11;19)(q23;p13.1) and t(11;19)(q23;p13.3): a cytogenetic and clinical profile of 53 patients. European 11q23 Workshop participants.

Moorman AV, Hagemeijer A, Charrin C, Rieder H, Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 805-810.

PMID 9593285

General Report on the European Union Concerted Action Workshop on 11q23, London, UK, May 1997.

Secker-Walker LM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1998 ; 12 (5) : 776-778.

PMID 9593280

Nineteen cases of the t(1;22)(p13;q13) acute megakaryblastic leukaemia of infants/children and a review of 39 cases: report from a t(1;22) study group.

Bernstein J, Dastugue N, Haas OA, Harbott J, Heerema NA, Huret JL, Landman-Parker J, LeBeau MM, Leonard C, Mann G, Pages MP, Perot C, Pirc-Danoewinata H, Roitzheim B, Rubin CM, Slociak M, Viguie F

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 ; 14 (1) : 216-218.

PMID 10637500

Contributor(s)

Written	05-1999	Jean-Loup Huret

Citation

This paper should be referenced as such :

Huret JL . Infant leukaemias,Congenital leukaemias,Neonatal leukaemias. Atlas Genet Cytogenet Oncol Haematol. May 1999 . URL : http://AtlasGeneticsOncology.org/Anomalies/InfantLeukID1084.html

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